A DOX-loaded polymer micelle for effectively inhibiting cancer cells

A novel triblock polymer is synthesized and self-assembled with doxorubicin to form DOX-loaded micelles. The synthetic process involves the ring-opening polymerization, carboxylation and amidation reactions, and the structures are characterized. The drug release test indicated that the micelles have the ability to control the release of drugs. The cell uptake results indicated that the DOX-loaded micelles could enter cancer cells easily, and the cytotoxicity and apoptosis test confirmed that DOX-loaded micelles have a strong killing effect on tumor cells, while the blank micelles do not have cytotoxicity. Therefore, the novel polymer micelles are a promising carrier for delivery of anticancer drugs to enhance cancer treatment.

A novel triblock polymer is synthesized and self-assembled with doxorubicin to form DOX-loaded micelles.     

Spermine modified polymeric micelles with pH-sensitive drug release for targeted and enhanced antitumor therapy

Tumor targeting delivery of chemotherapeutic drugs by nanocarriers has been demonstrated to be a promising strategy for cancer therapy with improved therapeutic efficacy. In this work, we reported a novel type of active targeting micelle with pH-responsive drug release by using biodegradable poly(lactide)-poly(2-ethyl-2-oxazoline) di-block copolymers functionalized with spermine (SPM). SPM has been considered as a tumor binding ligand through its specific interaction with the polyamine transport system (PTS), a transmembrane protein overexpressed on various types of cancer cell, while its application in nano-drug delivery systems has rarely been explored. The micelles with spherical shape (∼110 nm) could load hydrophobic paclitaxel (PTX) with high capacity, and release the payload much faster at acidic pH (4.5–6.5) than at pH 7.4. This pH-responsive property assisted the rapid escape of drug from the endo/lysosome after internalization as demonstrated by confocal laser scanning microscopy images using coumarin-6 (Cou-6) as a fluorescent probe. With surface SPM modification, the micelles displayed much higher cellular uptake than SPM lacking micelles in various types of cancer cells, demonstrating tumor targeting ability. The uptake mechanism of SPM modified micelles was explored by flow cytometry, which suggested an energy-consuming sag vesicle-mediated endocytosis pathway. As expected, the micelles displayed significantly enhanced anti-cancer activity. This work demonstrates that SPM modified pH-sensitive micelles may be potential drug delivery vehicles for targeting and effective cancer therapy.

Tumor targeting delivery of SPM functionalized micelles via PTS binding and their endocytosis and pH-triggered endo/lysosome drug release for anti-cancer therapy.     

Effect of solvophobicity on the phase behavior of linear ABC triblock copolymers in selective solvents: a Monte Carlo study

The microphase separation behavior of linear ABC triblock copolymers in A-selective solvents are studied using Monte Carlo simulation. The ABC triblock copolymer used in this study has a short solvophilic block A and two long solvophobic blocks B and C. The effects of the solvophobicity difference and the incompatibility between solvophobic blocks B and C on the micelle morphologies formed by linear ABC triblock copolymers are investigated, and phase diagrams as a function of the solvophobicity of blocks B and C are given at different repulsions between blocks B and C, respectively. A series of multicompartment micelles with distinct solvophobic parts is obtained, such as pupa-like multi-layered micelles, hamburger-like micelles and bumpy disks. Remarkably, when the solvophobicity of blocks B is much stronger than that of blocks C, a novel reverse core–shell–corona micelle with solvophilic blocks A located in the center of the micelle is obtained. Moreover, the results indicate that the competition between the effects of the incompatibility and solvophobicity difference between blocks B and C determines the microphase separation structures in the multicompartment micelles. These simulation results elucidate the mechanism of the formation of ABC triblock copolymer nanostructures and provide theoretical guidance for experimental studies.

The solvophobicity difference and incompatibility between different solvophobic blocks determine the overall shapes and micro-structures of micelles formed by linear ABC terpolymers.     

Formation of disk-like micelles of triblock copolymers in frustrating solvents

Coil–coil block copolymers rarely self-assemble into flat low-curvature micelles due to the lack of proper interchain association. Here, we report a facile route to prepare disk-like micelles through the self-assembly of amphiphilic polystyrene-b-polybutadiene-b-poly(2-vinylpyridine) triblock copolymers in a mixture of acetone and cyclohexane, which shows distinct selectivity towards the PS, PB and P2VP blocks. Subtle solvation/aggregation of these blocks in this frustrating solvent system provides access to low-curvature micellar structures, and thus favors the formation of uniform disk-like micelles. Further variation of the volume ratio of the mixed solvents also leads to the emergence of other interesting morphologies, including disk arrays, disk clusters and perforated disk-like micelles. This work provides a complementary insight into the solution self-assembly of block copolymers in a view of selective solvents and demonstrates a distinctive pathway to unconventional micellar nanostructures through the use of complex solvent systems.

Self-assembly of amphiphilic triblock copolymers in a frustrating solvent system leads to the formation of various low-curvature micellar structures.     

Polymer encapsulation of anticancer silver–N-heterocyclic carbene complexes

Amphiphilic block copolymers have been developed for the encapsulation of organometallic drugs. silver–N-heterocyclic carbene complexes have shown significant promise as anticancer and antibacterial compounds, and have been studied as the payload in these carriers. Simple modification of the N-heterocyclic carbene ligand structure enables solubility properties and interaction with the polymer to be tuned.

Amphiphilic block copolymers have been developed for the encapsulation of silver anticancer drugs.     

Effect of triblock copolymers on crystal growth and the photocatalytic activity of anatase TiO2 single crystals

In order to evaluate the effect of a triblock copolymer on the growth of TiO₂ crystals, anatase TiO₂ crystals with different morphologies and structures were synthesized by controlling the content and type of triblock copolymer in the solvothermal route. The resulting samples were characterized by XRD, XPS, SEM, TEM and EDX. The characterization results show that hydrofluoric acid can promote the formation of highly active (001) facets by the formation of a Ti–F bond. The triblock copolymers (P123 and F127) refine the surface structure of polycrystalline spherical TiO₂ and make the crystal surface homogeneous and smooth. Moreover, P123 causes the agglomeration effect and hinders the recrystallization process of anatase TiO₂ single crystals, and this will lead to corrosion of the crystal facets. Meanwhile, F127 destroys crystal formation and hinders crystal growth due to its special micelle structure. In addition, research on the photocatalytic activity proposed that the integrity of the (001) and (101) facets was a critical factor in the photocatalytic reaction. The resultant anatase TiO₂ single crystals could produce more hydroxyl radicals (˙OH) in the photocatalytic system, which exhibited remarkable photocatalytic performance for the degradation of three types of dye.

The effects of triblock copolymers (P123 and F127) on the growth of TiO₂ crystals were studied. Anatase TiO₂ crystals with different morphologies and structures were synthesized by controlling the content and type of triblock copolymer in a solvothermal method.     

Pluronic F127 self-assembled MoS2 nanocomposites as an effective glutathione responsive anticancer drug delivery system

In this study, bio-responsive polymeric MoS₂ nanocomposites were prepared for use as a drug carrier for cancer therapy. Herein, we report the synthesis and demonstrate the self-assembly of pluronic F127 (PF127) on a cystamine–glutathione–MoS₂ (CYS–GSH–MoS₂) system, which can be used for GSH-triggered drug release under biological reducing conditions. The reduction-sensitive disulfide bond containing CYS was incorporated between the amphiphilic copolymer PF127 and GSH–MoS₂ to achieve feasible drug release. Percent drug loading capacity and encapsulation efficiency were 51.3% and 56%, respectively. In addition, when the MoS₂–GSH–CYS–PF127 nanocomposite was incubated in a GSH environment, the morphology of the nanocomposite tended to change, ultimately leading to drug release. The drug-loaded PF127–CYS–GSH–MoS₂ polymeric nanocomposites efficiently released 52% of their drug content after 72 h of incubation in a GSH reduction environment. The HeLa cells treated with DOX loaded MoS₂–GSH–CYS–PF127 showed 38% toxicity at drug concentration of 40 μg, which indicated that the successfully released of drug from carrier and caused the cell death. Further, fluorescence microscopy images of HeLa cells revealed the potential behavior of the MoS₂–GSH–CYS–PF12 nanocomposite during the 2- and 4 h incubation periods; the nanocomposite was only found in the cytoplasm of HeLa cells. Interestingly, after 6 h of incubation, the drug was slowly released from the nanocomposite and could enter the nucleus as confirmed by fluorescence imaging of HeLa cells. Altogether, our synthesized PF127-coated MoS₂ nanocomposite could be effectively adopted in the near future as a GSH-sensitive drug carrier.

In this study, bio-responsive polymeric MoS₂ nanocomposites were prepared for use as a drug carrier for cancer therapy.     

Exchange dynamics between amphiphilic block copolymers and lipidic membranes through hydrophobic pyrene probe transfer

Vectorization has experienced significant development over the last few years and has been used to control the distribution of active ingredients to a target by their association with a vector. However, controlled drug delivery suffers from “burst release” as the drugs are released before the targeted site. Very few studies have examined the collective mechanisms of fission–fusion on micelles in the transport and expulsion of active ingredients. Endocytosis and exocytosis of cells are examples of fusion and fission in biological matter. Understanding these dynamics becomes crucial for the design and the control of new materials and new processes effective in controlled drug delivery. In this work, a study of the exchange dynamics between amphiphilic block copolymers and lipid membranes for vectorization of hydrophobic molecules using a fluorescence technique is presented. A highly hydrophobic alkylated pyrene, PyC₁₈, is used as a fluorescent probe that can be exchanged between amphiphilic block copolymer micelles and liposomes via different mechanisms. It is demonstrated that the exchange dynamics evaluated for different liposome concentrations is a collective mechanism characterized by having two rate constants.

Exchange dynamics between P104 micelles and liposomes for vectorization followed by using PyC₁₈ hydrophobic probe.     

Folic acid modified Fe3O4 nanoclusters by a one-step ultrasonic technique for drug delivery and MR imaging

Multifunctional nanoclusters based on Fe₃O₄ nanoparticles for magnetic resonance imaging (MRI) and drug delivery are reported here. At first, oleic acid (OA)-coated Fe₃O₄ nanoparticles were prepared. Then block copolymer Pluronic F127 or folic acid (FA) conjugated-Pluronic F127 was used to modify the hydrophobic nanoparticles to become hydrophilic Fe₃O₄@F127 nanoclusters via facile ultrasonic treatment. During this process, drug molecules can also be introduced into the nanoclusters and therefore the targeted drug delivery system was formed. Next, we verified the feasibility of the nanoclusters as drug delivery vehicles and magnetic contrast agents. The nanoclusters have an average size of 200 nm and remained stable in water for long periods. Folic acid-modified nanoclusters showed an enhanced intracellular uptake into HepG2 cells by using both cellular iron amount analysis and flow cytometry analysis. Besides, Fe₃O₄@F127@FA nanoclusters showed good compatibility in the tested concentration range and good sensitivity in T₂-weighted MRI. The magnetic nanoclusters combined with drug delivery properties have greatly increased the significance in the diagnosis and therapy of diseases, which are suitable for systematical administration of hydrophobic drugs and simultaneously MRI diagnosis.

Water-soluble Fe₃O₄@F127@FA nanoclusters were prepared by a facile ultrasonic-treated method for MR imaging and targeted drug delivery.     

Application progress of RVG peptides to facilitate the delivery of therapeutic agents into the central nervous system

The incidence of central nervous system (CNS) diseases is increasing with the aging population. However, it remains challenging to deliver drugs into the CNS because of the existence of a blood–brain barrier (BBB). Notably, rabies virus glycoprotein (RVG) peptides have been developed as delivery ligands for CNS diseases. So far, massive RVG peptide modified carriers have been reported, such as liposomes, micelles, polymers, exosomes, dendrimers, and proteins. Moreover, these drug delivery systems can encapsulate almost all small molecules and macromolecule drugs, including siRNA, microRNAs, DNA, proteins, and other nanoparticles, to treat various CNS diseases with efficient and safe drugs. In this review, targeted delivery systems with RVG peptide modified carriers possessing favorable biocompatibility and delivery efficiency are summarized.

Rabies virus glycoprotein (RVG) peptides have been developed to deliver drugs for CNS diseases. In the present review, RVG-mediated drug delivery systems are summarised, which can deliver almost all small molecules and macromolecule agents.     

Mechanistic insights into encapsulation and release of drugs in colloidal niosomal systems: biophysical aspects

Vesicular systems such as niosomes provide an alternative to improve drug delivery systems. The efficiency of a drug delivery vehicle is strongly dependent on its components which decide its interaction with partitioned drug(s) and locus of site of partitioning. A quantitative understanding of the physical chemistry underlying partitioning of drugs in complex systems of self-assemblies such as niosomes is scarcely available. In order to obtain quantitative mechanistic insights into partitioning and release of drugs [mitoxantrone (MTX) and ketoprofen (KTP)] in systems of niosomes, we have employed ultrasensitive calorimetry, spectroscopy and microscopy to establish correlations between functionality and energetics which could provide guidance towards rational drug design and choice of suitable non-ionic surfactant-based drug delivery vehicles. Electron microscopy and dynamic light scattering (DLS) methods were used for characterization and assessing the morphology of niosomes. We present here a calorimetry-based approach in assessing the partitioning of the anticancer drugs mitoxantrone and ketoprofen in niosomes and their release to human serum albumin (HSA) employing isothermal titration calorimetry (ITC), differential scanning calorimetry (DSC) and comparison with equilibrium dialysis. The thermodynamic signatures and kinetics of release were analyzed to obtain insights into the role of the functional groups on the drugs in the partitioning process. The assessment of thermal and conformational stability of proteins during drug binding and the effect of drug delivery vehicles on proteins is also crucial. To assess these effects, DSC studies on HSA in the presence and absence of drugs and niosomes were also performed. Finally, the efficacy of the system to impact the cell viability of the MDA-MB-231 triple-negative breast carcinoma cell line was analysed using MTT assay.

Vesicular systems such as niosomes provide an alternative to improve drug delivery systems.     

Dissolving microneedles delivering cancer cell membrane coated nanoparticles for cancer immunotherapy

Recently, a variety of tumor vaccines and immune system stimulators such as toll-like receptor (TLR) agonists have been widely investigated for cancer immunotherapy via transdermal delivery. Despite these great research efforts, low efficiency and discomfort remain a huge technical hurdle for the development of immunotherapeutics. Here, we design a facile method to deliver drugs to the skin through microneedles (MNs) to stimulate the immune system in two ways. As one of the tumor vaccines, cancer cell membrane proteins can act as tumor-specific antigens that are presented to antigen presenting cells (APCs) to activate the immune system. In addition, a toll-like receptor 7 (TLR7) agonist of imiquimod (R837) can suppress cancer cell growth by inhibiting angiogenesis. Using poloxamer 407 (F127) as a nanocarrier, F127 nanoparticles (F127 NPs) are loaded with R837 and then coated with cancer cell membranes (M). These F127–R837@M NPs are loaded in rapidly dissolving MNs and delivered through the skin. MNs loaded with F127–R837@M NPs show significant inhibition of cancer cell growth in both prophylactic vaccination and antitumor immunotherapy in vivo. The dual immune system stimulating F127–R837@M NPs could be effectively used for cancer immunotherapy.

Recently, a variety of tumor vaccines and immune system stimulators such as toll-like receptor (TLR) agonists have been widely investigated for cancer immunotherapy via transdermal delivery.     

Co-delivery of anti-PLK-1 siRNA and camptothecin by nanometric polydiacetylenic micelles results in a synergistic cell killing

Recently, it has been shown that the efficiency of antitumoral drugs can be enhanced when combined with therapeutic siRNAs. In the present study, an original platform based on polydiacetylenic micelles containing a cationic head group able to efficiently deliver a small interfering RNA (siRNA) targeting the PLK-1 gene while offering a hydrophobic environment for encapsulation of lipophilic drugs such as camptothecin is developed. We demonstrate that the co-delivery of these two agents with our micellar system results in a synergistic tumor cell killing of cervical and breast cancer cell lines in vitro. The combined drugs are active in a subcutaneous in vivo cancer model. Altogether, the results show that our nanometric micellar delivery system can be used for the development of new drug–siRNA combo-therapies.

Recently, it has been shown that the efficiency of antitumoral drugs can be enhanced when combined with therapeutic siRNAs.     

Functionalization and metathesis polymerization induced self-assembly of an alternating copolymer into giant vesicles

A facile fabrication of spherical vesicles and micelles by acyclic diene metathesis (ADMET) polymerization and alternative metathesis polymerization (ALTMET) was investigated. We utilize fluorine (FL) and perylene diimide-based (PDI) α,ω-dienes and α,ω-diacrylates to provide a series of homopolymers and alternating copolymers. When using α,ω-dienes as model monomers, TEM measurement indicates that the aromatic FL and PDI building block induced polymers to generate medium-sized (30–50 nm and 90–120 nm, respectively) micelles and vesicles. It was amazing that alternating copolymers derived from PDI α,ω-dienes and FL α,ω-diacrylates spontaneously form giant vesicles with sizes in the range of 0.7 μm to 2.5 μm. The controlled self-assembly of the organic polymer mediated by ADMET and ALTMET techniques avoided extremely annoying post treatment. Therefore, this work establishes a new, versatile synthetic strategy to create nanoparticles having tunable morphologies with potential application as molecular payload delivery vehicles.

Fluorine (FL) and perylene diimide-based (PDI) α,ω-dienes and α,ω-diacrylates were used to synthesise a series of homopolymers and alternating copolymers and provide spherical vesicles and micelles by metathesis polymerization.     

Dissipative particle dynamics simulation of multicompartment micelle nanoreactor with channel for reactants

The structural variation of multicompartment micelles is investigated using a dissipative particle dynamics simulation method for nano-reactor application. It turns out that well-defined multicompartment micelles with channel structures can be generated through the self-assembly of triblock copolymers consisting of a hydrophilic (A), a lipophilic (B), and a fluorophobic (C) block arranged in a B–A–C sequence: The corona and core are formed by the hydrophilic A block and the fluorophilic C block, respectively while the channel between the aqueous phase and core is formed by the lipophilic B block and the core. By performing a set of simulations, it is confirmed that channel size can be controlled as a function of the block length ratios between blocks A and B. Furthermore, it is also confirmed that the reactants pass through such channels to reach the micelle core by analyzing the pair correlation functions. By monitoring the change of the number of reactants in the multicompartment micelle, it is revealed that the diffusion of reactants into the core is slowed down as the concentration gradient is decreased. This work provides mesoscopic insight for the formation of multicompartment micelles and transport of reactants for use in the design of micelles as nanoreactors.

The structural variation of multicompartment micelles is investigated using a dissipative particle dynamics simulation method for nano-reactor application.     

Facile fabrication of water-dispersible nanocomposites based on hexa-peri-hexabenzocoronene and Fe3O4 for dual mode imaging (fluorescent/MR) and drug delivery

The facile fabrication of multifunctional nanocomposites (Fe₃O₄/HBC@F127) consisting of superparamagnetic Fe₃O₄ nanoparticles and fluorescent organic hexa-peri-hexabenzocoronene (HBC) molecules incorporated in block copolymer diacylphospholipid–polyethyleneglycol F127 have been demonstrated for dual mode imaging (fluorescent/MR) and drug delivery. The obtained nanocomposites were water-dispersible, stable and biocompatible, as confirmed by dynamic light scattering (DLS) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Relativity measurements showed a T₂ relaxivity (r₂) of 214.61 mM⁻¹ s⁻¹, which may be used as T₂-weighted MR imaging agents. In vitro imaging studies indicated that the nanocomposites had good MR and fluorescence imaging effects with low cytotoxicity. Besides, the developed nanocomposites could also be applied as drug delivery vehicles. Doxorubicin (DOX) loaded Fe₃O₄/HBC@F127 nanocomposites significantly inhibited the growth of human hepatoma cells (HepG2). These findings suggested that the facile synthesized multifunctional nanocomposites may be used as a platform for dual mode imaging (both MR and fluorescence) and drug delivery.

Water-dispersible, stable and biocompatible dandelion-like Fe₃O₄/HBC@F127 nanocomposites were facilely developed for dual mode imaging (fluorescent/MR) and drug delivery.     

Dual responsive PMEEECL–PAE block copolymers: a computational self-assembly and doxorubicin uptake study

The self-assembly behaviour of dual-responsive block copolymers and their ability to solubilize the anticancer drug doxorubicin (DOX) has been investigated using all-atom molecular dynamics (MD) simulations, MARTINI coarse-grained (CG) force field simulation and Scheutjens–Fleer self-consistent field (SCF) computations. These diblock copolymers, composed of poly{γ-2-[2-(2-methoxyethoxy)ethoxy]ethoxy-ε-caprolactone} (PMEEECL) and poly(β-amino ester) (PAE) are dual-responsive: the PMEEECL block is thermoresponsive (becomes insoluble above a certain temperature), while the PAE block is pH-responsive (becomes soluble below a certain pH). Three MEEECL₂₀–AE_M compositions with M = 5, 10, and 15, have been studied. All-atom MD simulations have been performed to calculate the coil-to-globule transition temperature (T_cg) of these copolymers and finding appropriate CG mapping for both PMEEECL–PAE and DOX. The output of the MARTINI CG simulations is in agreement with SCF predictions. The results show that DOX is solubilized with high efficiency (75–80%) at different concentrations inside the PMEEECL–PAE micelles, although, interestingly, the loading efficiency is reduced by increasing the drug concentration. The non-bonded interaction energy and the RDF between DOX and water beads confirm this result. Finally, MD simulations and SCF computations reveal that the responsive behaviour of PMEEECL–PAE self-assembled structures take place at temperature and pH ranges appropriate for drug delivery.

The self-assembly behaviour of dual-responsive block copolymers and their ability to solubilize the drug doxorubicin is demonstrated using molecular dynamics simulations, coarse-grained force field simulations and self-consistent field theory.     

Preparation of biocompatible hydrogels reinforced by different nanosheets

The impact of inorganic nanosheets with various chemical compositions and properties at different concentrations on the rheological properties and the gelation formation of a thermo-responsive hydrogel was investigated. F127 Pluronic triblock copolymers, with the structure (EO)₉₉(PO)₆₅(EO)₉₉ (EO: ethylene oxide and PO propylene oxide respectively), functionalized by dimethacrylate (F127-DMA) at a concentration of 25% was used in this study. After careful characterization by complementary techniques: transmission electron microscopy (TEM), atomic force microscopy (AFM), and X-ray diffraction of nanosheets derived from the peeling of layered materials (montmorillonite, organoclays and hexaniobate), the nanosheets were seen to be suitably dispersed in the hydrogels. The inclusion of hydrophobic nanosheets (i.e. those treated with the grafting of surfactants onto their surface: organoclays and hexaniobate) leads to a depression of the gelation temperature while the nanocomposites exhibit an enhancement of their elastic properties, as determined by rheological measurements. In contrast, the inclusion of hydrophilic nanosheet derived from raw montmorillonite engenders an opposite trend. The whole nanocomposites whose gelation temperature can be tuned by both the nature and concentration of the nanosheets were successfully photopolymerized allowing the formation of a 3D structure containing a large content of water. The results obtained in this study open new perspectives for possible uses of hydrogel-based nanocomposites as embedding matrixes for bio-organisms.

Inclusion of different nanosheets derived from layered materials as a way to control the gelation of a hydrogel based on F127 tri-block copolymers functionalized with dimethacrylate (127-DMA).     

Clinical developments of antitumor polymer therapeutics

Polymer therapeutics encompasses polymer–drug conjugates that are nano-sized, multicomponent constructs already in the clinic as antitumor compounds, either as single agents or in combination with other organic drug scaffolds. Nanoparticle-based polymer-conjugated therapeutics are poised to become a leading delivery strategy for cancer treatments as they exhibit prolonged half-life, higher stability and selectivity, water solubility, longer clearance time, lower immunogenicity and antigenicity and often also specific targeting to tissues or cells. Compared to free drugs, polymer-tethered drugs preferentially accumulate in the tumor sites unlike conventional chemotherapy which does not discriminate between the cancer cells and healthy cells, thereby causing severe side-effects. It is also desirable that the drug reaches its site of action at a particular concentration and the therapeutic dose remains constant over a sufficiently long period of time. This can be achieved by opting for new formulations possessing polymeric systems of drug carriers. However, many challenges still remain unanswered in polymeric drug conjugates which need to be readdressed and therefore, can broaden the scope of this field. This review highlights some of the antitumor polymer therapeutics including polymer–drug conjugates, polymeric micelles, polymeric liposomes and other polymeric nanoparticles that are currently under investigation.

Polymer therapeutics encompasses polymer–drug conjugates that are nano-sized, multicomponent constructs already in the clinic as antitumor compounds, either as single agents or in combination with other organic drug scaffolds.     

Synthesis of crosslinkable diblock terpolymers PDPA-b-P(NMS-co-OEG) and preparation of shell-crosslinked pH/redox-dual responsive micelles as smart nanomaterials

Crosslinked polymer nanomaterials have attracted great attention due to their stability and highly controllable drug delivery; herein, a series of well-defined amphiphilic PDPA-b-P(NMS-co-OEG) diblock terpolymers (P1–P3) were designed and prepared via RAFT polymerization and were self-assembled into non-cross-linked (NCL) nanomicelles, which were further prepared into shell-cross-linked (SCL) micelles via cystamine-based in situ shell cross-linking. Using P3 as an optimized polymer, SCL-P3 micelles were prepared, which demonstrated remarkable pH/redox-dual responsive behaviour. For drug delivery, camptothecin (CPT)-loaded SCL-P3 micelles were prepared and showed much higher CPT-loading capability than their NCL-P3 counterparts. Notably, the SCL-P3 micelles showed good synergistic pH/redox-dual responsive CPT release properties, making them potential “smart” nanocarriers for drug delivery.

A series of well-defined amphiphilic PDPA-b-P(NMS-co-OEG) diblock terpolymers were prepared via RAFT polymerization and self-assembled into non-cross-linked nanomicelles, and then shell-cross-linked micelles via cystamine-based in situ shell cross-linking.