Photosensitizer-assembled PEGylated graphene-copper sulfide nanohybrids as a synergistic near-infrared phototherapeutic agent

Objectives: Stimulative nanostructures play a crucial role in developing the smart nanomedicine for high therapeutic efficacy with minimum adverse effects. Herein, a near-infrared (NIR) light-responsive nanohybrids p-nanographene oxide (GO)-copper sulfide (CuS)/indocyanine green (ICG) comprised of GO, CuS nanoparticles and photosensitizer ICG was fabricated to couple the photothermal property of CuS and photodynamic effect of ICG in one system in order to achieve the synergistic phototherapy.

Methods: pGO-CuS/ICG was constructed by self-assembling ICG on pGO-CuS nanostructure. Its physicochemical, photothermal and photodynamic properties were studied by spectroscopic methods. The in vitro cellular uptake, cytotoxicity, the single/combined photothermal therapeutic (PTT) and photodynamic therapeutic (PDT) effects were investigated with biological techniques.

Results: pGO-CuS/ICG exhibited high efficacy of photothermal conversation and singlet oxygen generation under NIR laser excitation. It entered into the target cancer cells probably via passive transmembrane pathway and exerted obvious PTT and PDT effect against the tumor cells upon irradiation with the respective 940 and 808 nm lasers. In particular, the tremendous synergistic efficacy of PDT and PTT had been demonstrated by tuning the NIR laser combined irradiation.

Conclusions: This study promises the future applications of pGO-CuS/ICG as a NIR light activable theranostic nanodrug for deep-seated cancer noninvasive phototherapy.     

Folate-receptor-targeted delivery of docetaxel nanoparticles prepared by PLGA–PEG–folate conjugate

For folate-receptor-targeted anticancer therapy, docetaxel (DTX) nanoparticles (NPs) were produced employing polylactide-co-glycolide–polyethylene glycol–folate (PLGA–PEG–FOL) conjugate. The FOL-conjugated di-block copolymer was synthesized by coupling the PLGA–PEG–NH₂ di-block copolymer with an activated folic acid. It was expected that FOL moieties were exposed on the micellar surface.

The conjugates assisted in the formation of DTX NPs with an average size of 200 nm in diameter through an emulsification/solvent diffusion method. The FOL-targeted NPs showed a greater extent of intracellular uptake in FOL-receptor-positive cancer cells (SKOV3) in comparison with the non-targeted NPs, indicating that the FOL-receptor-mediated endocytosis mechanism could have a role in the cellular uptake of NPs. These results suggested that FOL-targeted DTX NPs could be a potentially useful delivery system for FOL-receptor-positive cancer cells.     

Self-delivering prodrug-nanoassemblies fabricated by disulfide bond bridged oleate prodrug of docetaxel for breast cancer therapy

Breast cancer leads to high mortality of women in the world. Docetaxel (DTX) has been widely applied as one of the first-line chemotherapeutic drugs for breast cancer therapy. However, the clinical outcome of DTX is far from satisfaction due to its poor drug delivery efficiency. Herein, a novel disulfide bond bridged oleate prodrug of DTX was designed and synthesized to construct self-delivering prodrug-based nanosystem for improved anticancer efficacy of DTX. The uniquely engineered prodrug-nanoassemblies showed redox-responsive drug release, increased cellular uptake and comparable cytotoxicity against 4T1 breast cancer cells when compared with free DTX. In vivo, oleate prodrug-based nanoparticles (NPs) demonstrated significantly prolonged systemic circulation and increased accumulation in tumor site. As a result, prodrug NPs produced a notable antitumor activity in 4T1 breast cancer xenograft in BALB/c mice. This prodrug-based self-assembly and self-delivery strategy could be utilized to improve the delivery efficiency of DTX for breast cancer treatment.     

Co-delivery of docetaxel and bortezomib based on a targeting nanoplatform for enhancing cancer chemotherapy effects

Using facile polydopamine (PDA)-based surface modification and a pH-sensitive catechol-boronate binding mechanism, a novel drug delivery system was designed for the treatment of breast cancer. The system was able to achieve the following goals: active targeting, pH responsiveness, in vivo blood circulation for a prolonged period of time, and dual drug loading. After coating with PDA, the docetaxel (DTX)-loaded star-shaped copolymer cholic acid-poly(lactide-co-glycolide) nanoparticles (CA-PLGA@PDA/NPs) were functionalized with amino-poly(ethylene glycol)-folic acid (NH₂-PEG-FA) and bortezomib (BTZ) to form the targeting composition, DTX-loaded CA-PLGA@PDA-PEG-FA?+?BTZ/NPs. The novel NPs exhibited similar drug release characteristics compared to unfunctionalized CA-PLGA/NPs. Meanwhile, the incorporated NH₂-PEG-FA contributed to active targeting which was illustrated by cellular uptake experiments and biodistribution studies. Moreover, the pH responsive binding between BTZ and PDA was demonstrated to be effective to release BTZ at the tumor acidic environment for synergistic action with DTX. Both in vitro cytotoxicity and in vivo antitumor studies demonstrated that the novel nanoplatform exhibited the most suitable therapeutic effects. Taken together, the versatile PDA modified DTX-loaded CA-PLGA@PDA-PEG-FA?+?BTZ/NPs offered a promising chemotherapeutic strategy for enhancing breast cancer treatment.     

Multi-responsive nanotheranostics with enhanced tumor penetration and oxygen self-producing capacities for multimodal synergistic cancer therapy

Incorporation of multiple functions into one nanoplatform can improve cancer diagnostic efficacy and enhance anti-cancer outcomes. Here, we constructed doxorubicin (DOX)-loaded silk fibroin-based nanoparticles (NPs) with surface functionalization by photosensitizer (N770). The obtained nanotheranostics (N770-DOX@NPs) had desirable particle size (157 nm) and negative surface charge (?25 mV). These NPs presented excellent oxygen-generating capacity and responded to a quadruple of stimuli (acidic solution, reactive oxygen species, glutathione, and hyperthermia). Surface functionalization of DOX@NPs with N770 could endow them with active internalization by cancerous cell lines, but not by normal cells. Furthermore, the intracellular NPs were found to be preferentially retained in mitochondria, which were also efficient for near-infrared (NIR) fluorescence imaging, photothermal imaging, and photoacoustic imaging. Meanwhile, DOX could spontaneously accumulate in the nucleus. Importantly, a mouse test group treated with N770-DOX@NPs plus NIR irradiation achieved the best tumor retardation effect among all treatment groups based on tumor-bearing mouse models and a patient-derived xenograft model, demonstrating the unprecedented therapeutic effects of trimodal imaging-guided mitochondrial phototherapy (photothermal therapy and photodynamic therapy) and chemotherapy. Therefore, the present study brings new insight into the exploitation of an easy-to-use, versatile, and robust nanoplatform for programmable targeting, imaging, and applying synergistic therapy to tumors.     

Manganese-containing polydopamine nanoparticles as theranostic agents for magnetic resonance imaging and photothermal/chemodynamic combined ferroptosis therapy treating gastric cancer

Gastric cancer (GC) is a serious disease with high morbidity and mortality rates worldwide. Chemotherapy plays a key role in GC treatment, while inevitable drug resistance and systematic side effects hinder its clinical application. Fenton chemistry-based chemodynamic therapy (CDT) has been used as a strategy for cancer ferroptosis, and the CDT efficiency could be enhanced by photothermal therapy (PTT). With the trend of treatment and diagnosis integration, the combination of magnetic resonance imaging (MRI) and CDT/PTT exhibits enormous progress. Herein, we constructed a platform based on PEGylated manganese-containing polydopamine (PDA) nanoparticles, named as PEG-PDA@Mn (PP@Mn) NPs. The PP@Mn NPs were stable and globular. Furthermore, they demonstrated near-infrared (NIR)-triggered PTT and Fenton-like reaction-based CDT effects and T1-weighted MRI capabilities. According to in vitro studies, the PP@Mn NPs trigger ferroptosis in cancer cells by producing abundant reactive oxygen species (ROS) via a Fenton-like reaction combined with PTT. Furthermore, in vivo studies showed that, under MRI guidance, the PP@Mn NPs combined with the PTT at the tumor region, have CDT anti-tumor effect. In conclusion, the PP@Mn NPs could provide an effective strategy for CDT/PTT synergistic ferroptosis therapy for GC.     

Ceramide lipid-based nanosuspension for enhanced delivery of docetaxel with synergistic antitumor efficiency

Ceramide (CE), a bioactive lipid with tumor suppression, has been widely used as a drug carrier and enhancer for cancer therapy. CE-based combination therapy was prone to be attractive in cancer therapy. In our previous study, the combination of CE and docetaxel (DTX) was proved to be an effective strategy for cancer therapy. To further improve the antitumor efficiency of DTX, the CE lipid-based nanosuspensions (LNS) was prepared for the delivery of DTX to exhibit synergistic therapeutic effect. The enhanced delivery and synergistic therapeutic effect of DTX-loaded CE-LNS (CE?+?DTX-LNS) were evaluated. CE?+?DTX-LNS exhibited spherical or ellipsoidal shape, uniform particle size distribution (108.1?±?3.8?nm), sustained release characteristics and good stability in vitro. Notably, CE?+?DTX-LNS could effectively co-localize CE and DTX into same tumor cell and subsequently play synergistic cell damage effect compared with CE-LNS?+?DTX-LNS (p?in vivo fluorescence imaging results showed that CE?+?DTX-LNS could effectively prolong the in vivo circulation time and enhance the accumulation in tumor sites. Moreover, the antitumor efficacy of CE?+?DTX-LNS observed in B16 murine melanoma model was 93.94?±?2.77%, significantly higher than that of CE-LNS, DTX-LNS, Duopafei® (p?p?相似文献   

Development of redox-responsive theranostic nanoparticles for near-infrared fluorescence imaging-guided photodynamic/chemotherapy of tumor

The development of imaging-guided smart drug delivery systems for combinational photodynamic/chemotherapy of the tumor has become highly demanded in oncology. Herein, redox-responsive theranostic polymeric nanoparticles (NPs) were fabricated innovatively using low molecular weight heparin (LWMH) as the backbone. Chlorin e6 (Ce6) and alpha-tocopherol succinate (TOS) were conjugated to LMWH via cystamine as the redox-sensitive linker, forming amphiphilic Ce6-LMWH-TOS (CHT) polymer, which could self-assemble into NPs in water and encapsulate paclitaxel (PTX) inside the inner core (PTX/CHT NPs). The enhanced near-infrared (NIR) fluorescence intensity and reactive oxygen species (ROS) generation of Ce6 were observed in a reductive environment, suggesting the cystamine-switched “ON/OFF” of Ce6. Also, the in vitro release of PTX exhibited a redox-triggered profile. MCF-7 cells showed a dramatically higher uptake of Ce6 delivered by CHT NPs compared with free Ce6. The improved therapeutic effect of PTX/CHT NPs compared with mono-photodynamic or mono-chemotherapy was observed in vitro via MTT and apoptosis assays. Also, the PTX/CHT NPs exhibited a significantly better in anti-tumor efficiency upon NIR irradiation according to the results of in vivo combination therapy conducted on 4T1-tumor-bearing mice. The in vivo NIR fluorescence capacity of CHT NPs was also evaluated in tumor-bearing nude mice, implying that the CHT NPs could enhance the accumulation and retention of Ce6 in tumor foci compared with free Ce6. Interestingly, the anti-metastasis activity of CHT NPs was observed against MCF-7 cells by a wound healing assay, which was comparable to LMWH, suggesting LMWH was promising for construction of nanocarriers for cancer management.     

Near-infrared light-activated IR780-loaded liposomes for anti-tumor angiogenesis and Photothermal therapy

Tumor angiogenesis is a key step in the process of tumor development, and antitumor angiogenesis has a profound influence on tumor growth. Herein we report a dual-function drug delivery system comprising a Near-infrared (NIR) dye and an anti-angiogenic drug within liposomes (Lip-IR780-Sunitinib) for enhanced antitumor therapy. The hydrophobic NIR dye IR780 was loaded into the liposome phospholipid bilayer, and the bilayer would be disrupted by laser irradiation so that anti-angiogenic drug sunitinib release would be activated remotely at the tumor site. The released hydrophilic sunitinib could potentially target multiple VEGF receptors on the tumor endothelial cell surface to inhibit angiogenesis. Meanwhile, IR780-loaded liposomes kill the cancer cells by photothermal therapy. Lip-IR780-Sunitinib exhibited enhanced anti-tumor and anti-angiogenic effects in vitro and in vivo. This system facilitates easy and controlled release of cargos to achieve anti-tumor angiogenesis and photothermal therapy.     

Long circulating PEGylated poly(d,l-lactide-co-glycolide) nanoparticulate delivery of Docetaxel to solid tumors

Purpose: The aim of this study was to investigate the ability of PEGylated poly(d,l-lactide-co-glycolide) nanoparticles (NPs) to deliver Docetaxel (DTX) (an anticancer agent) to solid tumors.

Methods: PLGA–mPEG diblock copolymers were synthesized by ring opening polymerization reaction and characterized by ¹H NMR, FT-IR and gel permeation chromatography. NPs, with a smooth spherical shape and near 100 nm size were prepared using the emulsion solvent evaporation technique and characterized. The drug release rate was investigated in acidic and physiological media (phosphate buffer saline, pH 5.0 and 7.4). The therapeutic efficacy and biocompatibility of NP formulations were evaluated for in vitro cytotoxicity by MTT assay using MCF-7 and C26 cell lines. The pharmacokinetic and biodistribution studies were performed on C26 tumor bearing mice. The antitumor efficacy of DTX NP formulations on C26 tumor bearing mice was investigated.

Results: DTX-loaded PEGylated NPs increased the drug's biological half-life while providing substantial accumulation at the solid tumors. PEGylated NPs appear to be a promising alternate carrier for DTX having greater efficacy in inhibiting tumor growth.     

Polydopamine-coated i-motif DNA/Gold nanoplatforms for synergistic photothermal-chemotherapy

The combination of photothermal therapy with chemotherapy has gradually developed into promising cancer therapy. Here, a synergistic photothermal-chemotherapy nanoplatform based on polydopamine (PDA)-coated gold nanoparticles (AuNPs) were facilely achieved via the in situ polymerization of dopamine (DA) on the surface of AuNPs. This nanoplatform exhibited augmented photothermal conversion efficiency and enhanced colloidal stability in comparison with uncoated PDA shell AuNPs. The i-motif DNA nanostructure was assembled on PDA-coated AuNPs, which could be transformed into a C-quadruplex structure under an acidic environment, showing a characteristic pH response. The PDA shell served as a linker between the AuNPs and the i-motif DNA nanostructure. To enhance the specific cellular uptake, the AS1411 aptamer was introduced to the DNA nanostructure employed as a targeting ligand. In addition, Dox-loaded NPs (DAu@PDA-AS141) showed the pH/photothermal-responsive release of Dox. The photothermal effect of DAu@PDA-AS141 elicited excellent photothermal performance and efficient cancer cell inhibition under 808 nm near-infrared (NIR) irradiation. Overall, these results demonstrate that the DAu@PDA-AS141 nanoplatform shows great potential in synergistic photothermal-chemotherapy.     

Magnetic nanoparticles modified-porous scaffolds for bone regeneration and photothermal therapy against tumors

For effectively treating tumor related-bone defects, design and fabrication of multifunctional biomaterials still remain a great challenge. Herein, we firstly fabricated magnetic SrFe₁₂O₁₉ nanoparticles modified-mesoporous bioglass (BG)/chitosan (CS) porous scaffold (MBCS) with excellent bone regeneration and antitumor function. The as-produced magnetic field from MBCS promoted the expression levels of osteogenic-related genes (OCN, COL1, Runx2 and ALP) and the new bone regeneration by activated BMP-2/Smad/Runx2 pathway. Moreover, the SrFe₁₂O₁₉ nanoparticles in MBCS improved the photothermal conversion property. Under the irradiation of near-infrared (NIR) laser, the elevated temperatures of tumors co-cultured with MBCS triggered tumor apoptosis and ablation. As compared with the pure scaffold group, MBCS/NIR group possessed the excellent antitumor efficacy against osteosarcoma via the hyperthermia ablation. Therefore, the multifunctional MBCS with excellent bone regeneration and photothermal therapy functions has a great application for treating the tumor-related bone defects.     

Real-time SERS monitoring anticancer drug release along with SERS/MR imaging for pH-sensitive chemo-phototherapy

In situ and real-time monitoring of responsive drug release is critical for the assessment of pharmacodynamics in chemotherapy. In this study, a novel pH-responsive nanosystem is proposed for real-time monitoring of drug release and chemo-phototherapy by surface-enhanced Raman spectroscopy (SERS). The Fe₃O₄@Au@Ag nanoparticles (NPs) deposited graphene oxide (GO) nanocomposites with a high SERS activity and stability are synthesized and labeled with a Raman reporter 4-mercaptophenylboronic acid (4-MPBA) to form SERS probes (GO-Fe₃O₄@Au@Ag-MPBA). Furthermore, doxorubicin (DOX) is attached to SERS probes through a pH-responsive linker boronic ester (GO-Fe₃O₄@Au@Ag-MPBA-DOX), accompanying the 4-MPBA signal change in SERS. After the entry into tumor, the breakage of boronic ester in the acidic environment gives rise to the release of DOX and the recovery of 4-MPBA SERS signal. Thus, the DOX dynamic release can be monitored by the real-time changes of 4-MPBA SERS spectra. Additionally, the strong T₂ magnetic resonance (MR) signal and NIR photothermal transduction efficiency of the nanocomposites make it available for MR imaging and photothermal therapy (PTT). Altogether, this GO-Fe₃O₄@Au@Ag-MPBA-DOX can simultaneously fulfill the synergistic combination of cancer cell targeting, pH-sensitive drug release, SERS-traceable detection and MR imaging, endowing it great potential for SERS/MR imaging-guided efficient chemo-phototherapy on cancer treatment.     

Trimodal synergistic antitumor drug delivery system based on graphene oxide

A multifunctional antitumor drug delivery system was synthesized based on graphene oxide (GO) for near-infrared (NIR) light controlling chemotherapeutic/photothermal (PTT) /photodynamic (PDT) trimodal synergistic therapy. The system named ICG-Wed-GO was formed by co-loading wedelolactone (Wed) and indocyanine green (ICG) on the surface of GO through π–π stacking interaction. Under NIR laser irradiation, ICG-Wed-GO could effectively absorb and transform optical energy to heat, generate reactive oxygen species (ROS) to ablating and damage tumor cells. The temperature of ICG-Wed-GO solution reached up to 79.4?°C in 10?min with NIR irradiation. In in vitro and in vivo study, ICG-Wed-GO showed excellent antitumor effect. After 14-day treatment of ICG-Wed-GO with NIR laser irradiation, the tumor disappeared completely on tumor-bearing mice. The low biotoxicity of ICG-Wed-GO was also proved. The system achieved the synergistic trimodal chemotherapeutic/photothermal/photodynamic treatment and demonstrated excellent antitumor effect, which is expected to have a greater potential for cancer therapy.     

Targeted peptide-modified oxidized mesoporous carbon nanospheres for chemo-thermo combined therapy of ovarian cancer in vitro

Ovarian cancer remains one of serious hazards to human health due to many drawbacks of existing available treatment options. In this study, a multifunctional chemo-thermo combined therapy nanoplatform (OMCNPID) was successfully prepared, which is composed of I₆P₈ peptide as a targeting moiety to interleukin-6 receptors (IL-6Rs), oxidized mesoporous carbon nanospheres (OMCN) as a near infrared (NIR)-triggered drug carrier and doxorubicin (DOX) as a chemotherapeutic drug and fluorescent agent. The synthesized multifunctional nanoplatform displayed high storage capacity for drugs and excellent photothermal properties. Besides, DOX was rapidly released from OMCNPID at the condition of low pH and NIR laser irradiation due to the dissociation of DOX from graphitic cores of OMCN. In vitro experimental results verified that OMCNPID could be markedly taken up by SKOV-3 monolayer cells and tumor spheroids, and revealed a remarkable synergistic chemo-photothermal effect against ovarian cancer. All the results demonstrated that OMCNPID is a pH/NIR dual-stimulus responsive nanoplatform and can achieve efficient chemo-thermo combined therapy.     

Novel application of pluronic lecithin organogels (PLOs) for local delivery of synergistic combination of docetaxel and cisplatin to improve therapeutic efficacy against ovarian cancer

The synergistic combination of docetaxel (DTX) and cisplatin (CIS) by local drug delivery with a pluronic lecithin organogel (PLO) to facilitate high drug concentrations at tumor sites and less nonspecific distribution to normal organs is thought to be beneficial in chemotherapy. In this study, using Capryol-90 (C90) with the addition of lecithin as the oil phase was developed to carry DTX, which was then incorporated into a PLO-containing CIS to formulate a dual-drug injectable PLO for local delivery. An optimal PLO composite, P₁₃L_0.15O_1.5, composed of PF127:lecithin:C90 at a 13:0.15:1.5 weight ratio was obtained. The sol–gel transition temperature of P₁₃L_0.15O_1.5 was found to be 33?°C. Tumor inhibition studies illustrated that DTX/CIS-loaded P₁₃L_0.15O_1.5 could efficiently suppress tumor growth by both intratumoral and peritumoral injections in SKOV-3 xenograft mouse model. Pharmacokinetic studies showed that subcutaneous administration of P₁₃L_0.15O_1.5 was able to sustain the release of DTX and CIS leading to their slow absorption into the systemic circulation resulting in lower area under the plasma concentration curve at 0–72?h (AUC_0–72) and maximum concentration (C_max) values but longer half-life (T_1/2) and mean residence time (MRT) values. An in vivo biodistribution study showed lower DTX and CIS concentrations in organs compared to other treatment groups after IT administration of the dual drug-loaded P₁₃L_0.15O_1.5. It was concluded that the local co-delivery of DTX and CIS by PLOs may be a promising and effective platform for local anticancer drug delivery with minimal systemic toxicities.     

One-step preparation,characterization, and anticancer potential of ZnFe2O4/RGO nanocomposites

Zinc ferrite nanoparticles (ZnFe₂O₄ NPs) have attracted extensive attention for their diverse applications including sensing, waste-water treatment, and biomedicine. The novelty of the present work is the fabrication of ZnFe₂O₄/RGO NCs by using a one-step hydrothermal process to assess the influence of RGO doping on the physicochemical properties and anticancer efficacy of ZnFe₂O₄ NPs. X-ray diffraction (XRD), Scanning electron microscopy (SEM), Energy-dispersive X-ray(EDX), X-ray photoelectron spectroscopy (XPS), Fourier-transform infrared spectroscopy (FTIR), UV–vis spectroscopy, and Photoluminescence (PL) spectroscopy were employed to characterize prepared pure ZnFe₂O₄ NPs and ZnFe₂O₄/ RGO NCs. XRD results showed that the synthesized samples have high crystallinity. Furthermore, the average crystal sizes of ZnFe₂O₄ nanoparticles (NPs) and ZnFe₂O₄/RGO nanocomposites (NCs) were 51.08 nm and 54.36 nm, respectively. SEM images revealed that pure ZnFe₂O₄ NPs were spherical in shape with uniformly loaded on the surface of the RGO nanosheet. XPS and EDX analysis confirmed the elemental compositions of ZnFe₂O₄/RGO NCs. Elemental mapping of SEM shows that the elemental compositions (Zn, Fe, O, and C) were homogeneously distributed in ZnFe₂O₄/RGO NCs. The intensity of FT-IR spectra depicted that pure ZnFe₂O₄ NPs were successfully anchored into the RGO nanosheet. An optical study suggested that the band gap energy of ZnFe₂O₄/RGO NCs (1.61 eV) was lower than that of pure ZnFe₂O₄ NPs (1.96 eV). PL spectra indicated that the recombination rate of the ZnFe₂O₄/ RGO NCs was lower than ZnFe₂O₄ NPs. MTT assay was used to evaluate the anticancer performance of ZnFe₂O₄ /RGO NCs and pure ZnFe₂O₄NPs against human cancer cells. In vitro study indicates that ZnFe₂O₄ /RGO NCs have higher anticancer activity against human breast (MCF-7) and lung (A549) cancer cells as compared to pure form ZnFe₂O₄ NPs. This work suggests that RGO doping enhances the anticancer activity of ZnFe₂O₄NPs by tuning its optical behavior. This study warrants future research on potential therapeutic applications of these types of nanocomposites.     

NIR light-induced tumor phototherapy using photo-stable ICG delivery system based on inorganic hybrid

NIR responsive inorganic hybrid (Ti@GO) was synthesized. It could absorb NIR light and convert it into local hyperthermia and ROS synchronously. Ti@GO was firstly developed as a photosensitizer and a photothermal agent to realize tumor PTT and PDT. For anti-tumor application, HA was grafted on Ti@GO simultaneously as water solubility improver and tumor targeting moiety. ICG was chosen as a model drug. Results demonstrated that HA-Ti@GO could remarkably improve ICG stability and drug accumulation in 4T1 cells, enhance tumor phototherapy efficiency and reduce light-associated side effects. HA-Ti@GO/ICG under NIR laser irradiation showed a significant decreased cell viability of 20.7 ± 2.6% and a high DNA damage degree of 82.4 ± 8.3%. Moreover, in vivo results showed that HA-Ti@GO/ICG plus NIR laser achieved almost complete tumor regression on 4T1 tumor-bearing mice, with a tumor volume of 67.0 mm³. Taken together, our study provided a promising strategy to realize synergistic PTT/PDT tumor therapy with a single NIR light.     

Polyunsaturated fatty acid-based targeted nanotherapeutics to enhance the therapeutic efficacy of docetaxel

Since breast cancer is one of the most lethal malignancies, targeted strategies are urgently needed. In this study, we report the enhanced therapeutic efficacy of docetaxel (DTX) when combined with polyunsaturated fatty acids (PUFA) for effective treatment of multi-resistant breast cancers. Folic acid (FA)-conjugated PUFA-based lipid nanoparticles (FA-PLN/DTX) was developed. The physicochemical properties, in vitro uptake, in vitro cytotoxicity, and in vivo anticancer activity of FA-PLN/DTX were evaluated. FA-PLN/DTX could efficiently target and treat human breast tumor xenografts in vivo. They showed high payload carrying capacity with controlled release characteristics and selective endocytic uptake in folate receptor-overexpressing MCF-7 and MDA-MB-231 cells. PUFA synergistically improved the anticancer efficacy of DTX in both tested cancer cell lines by inducing a G2/M phase arrest and cell apoptosis. Combination of PUFA and DTX remarkably downregulated the expression levels of pro-apoptotic and anti-apoptotic markers, and blocked the phosphorylation of AKT signaling pathways. Compared to DTX alone, FA-PLN/DTX showed superior antitumor efficacy, with no signs of toxic effects in cancer xenograft animal models. We propose that PUFA could improve the therapeutic efficacy of anticancer agents in cancer therapy. Further studies are necessary to fully understand these findings and achieve clinical translation.     

Effective photothermal chemotherapy with docetaxel-loaded gold nanospheres in advanced prostate cancer

Background: Multifunctional gold nanospheres (MGNs)-loaded with docetaxel (MGN@DTX) were prepared and evaluated for therapeutic efficacy in nude mice bearing human prostate cancer xenografts.

Methods: MGNs were prepared from PEGylated hollow gold nanospheres (HGNs) coated with folic acid and DTPTT chelate. Then, the effect of radiolabelled MGNs (^99mTc-MGNs) on PC-3 cell apoptosis was assessed by flow cytometry, while their binding affinity to these cells was evaluated by cell binding assays. Next, biodistribution of ^99mTc-MGNs in xenograft bearing mice was measured by SPECT imaging. Also, DTX loading and release rates were estimated in MGN@DTX. Finally, in vitro stability in human serum and cytotoxicity of MGN@DTX were assessed, as well as their antitumor effect in xenograft bearing mice.

Results: ^99mTc-MGNs (97.69% purity) showed good binding affinity to PC-3 cells, a specific recognition blocked by excess folic acid. Interestingly, MGN@DTX remained stable in human serum for 24 h, and exhibited higher mean cytotoxicity after NIR laser irradiation than free DTX. By day 28, tumor inhibition rates were higher in the MGN@DTX?+?NIR laser irradiation group compared with the DTX and MGNs?+?NIR laser irradiation groups.

Conclusions: Loading chemotherapeutic drugs into MGNs can increase antitumor potency, reduce normal cell damage and decrease drug resistance, thus representing a promising approach for advanced prostate cancer treatment.