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.     

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.     

Iodinated cyanine dye-based nanosystem for synergistic phototherapy and hypoxia-activated bioreductive therapy

Photodynamic therapy (PDT) has been applied in cancer treatment by utilizing reactive oxygen species (ROS) to kill cancer cells. However, the effectiveness of PDT is greatly reduced due to local hypoxia. Hypoxic activated chemotherapy combined with PDT is expected to be a novel strategy to enhance anti-cancer therapy. Herein, a novel liposome (LCT) incorporated with photosensitizer (PS) and bioreductive prodrugs was developed for PDT-activated chemotherapy. In the design, CyI, an iodinated cyanine dye, which could simultaneously generate enhanced ROS and heat than other commonly used cyanine dyes, was loaded into the lipid bilayer; while tirapazamine (TPZ), a hypoxia-activated prodrug was encapsulated in the hydrophilic nucleus. Upon appropriate near-infrared (NIR) irradiation, CyI could simultaneously produce ROS and heat for synergistic PDT and photothermal therapy (PTT), as well as provide fluorescence signals for precise real-time imaging. Meanwhile, the continuous consumption of oxygen would result in a hypoxia microenvironment, further activating TPZ free radicals for chemotherapy, which could induce DNA double-strand breakage and chromosome aberration. Moreover, the prepared LCT could stimulate acute immune response through PDT activation, leading to synergistic PDT/PTT/chemo/immunotherapy to kill cancer cells and reduce tumor metastasis. Both in vitro and in vivo results demonstrated improved anticancer efficacy of LCT compared with traditional PDT or chemotherapy. It is expected that these iodinated cyanine dyes-based liposomes will provide a powerful and versatile theranostic strategy for tumor target phototherapy and PDT-induced chemotherapy.     

New-generation photosensitizer-anchored gold nanorods for a single near-infrared light-triggered targeted photodynamic–photothermal therapy

Traditional combined photodynamic and photothermal therapy (PDT/PTT) was limited in clinical treatment of cancer due to the exceptionally low drug delivery efficiency to tumor sites and the activation by laser excitation with different wavelengths. We have accidentally discovered that our synthesized chlorin e6-C-15-ethyl ester (HB, a new type of photosensitizer) be activated by a laser with an excitation wavelength of 660 nm. Herein, we utilized Au nanorods (AuNRs) as 660 nm-activated PTT carriers to be successively surface-functionalized with HB and tumor-targeting peptide cyclic RGD (cRGD) to develop HB-AuNRs@cRGD for single NIR laser-induced targeted PDT/PTT. The HB-AuNRs@cRGD could be preferentially accumulated within tumor sites and rapidly internalized by cancer cells. Thereby, the HB-AuNRs@cRGD could exhibit amplified therapeutic effects by producing both significant reactive oxygen species (ROS) and hyperthermia simultaneously under the guidance of fluorescence imaging. The tumor inhibition rate on ECA109 esophageal cancer model was approximately 77.04%, and the negligible systematic toxicity was observed. This study proposed that HB-AuNRs@cRGD might be a promising strategy for single NIR laser-induced and imaging-guided targeted bimodal phototherapy.     

Tumor microenvironment-responsive artesunate loaded Z-scheme heterostructures for synergistic photo-chemodynamic therapy of hypoxic tumor

Tumor microenvironment (TME) with the particular features of severe hypoxia, insufficient endogenous H₂O₂, and overexpression of glutathione (GSH) markedly reduced the antitumor efficacy of monotherapy. Herein, a TME-responsive multifunctional nanoplatform (Bi₂S₃@Bi@PDA-HA/Art NRs) was presented for synergistic photothermal therapy (PTT), chemodynamic therapy (CDT), and photodynamic therapy (PDT) to achieve better therapeutic outcomes. The Z-scheme heterostructured bismuth sulfide@bismuth nanorods (Bi₂S₃@Bi NRs) guaranteed excellent photothermal performance of the nanoplatform. Moreover, its ability to produce O₂ and reactive oxygen species (ROS) synchronously could relieve tumor hypoxia and improve PDT outcomes. The densely coated polydopamine/ammonium bicarbonate (PDA/ABC) and hyaluronic acid (HA) layers on the surface of the nanoplatform enhanced the cancer-targeting capacity and induced the acidic TME-triggered in situ “bomb-like” release of Art. The CDT treatment was achieved by activating the released Art through intracellular Fe²⁺ ions in an H₂O₂-independent manner. Furthermore, decreasing the glutathione peroxidase 4 (GPX4) levels by Art could also increase the PDT efficiency of Bi₂S₃@Bi NRs. Owing to the synergistic effect, this nanoplatform displayed improved antitumor efficacy with minimal toxicity both in vitro and in vivo. Our design sheds light on the application of phototherapy combined with the traditional Chinese medicine monomer-artesunate in treating the hypoxic tumor.     

Folic acid-modified and functionalized CuS nanocrystal-based nanoparticles for combined tumor chemo- and photothermal therapy

Recent studies have identified that CuS nanocrystal (CuS NCs) could be used as a new class of promising photo-thermal agents due to their excellent plasmonic absorption abilities in a wide near-infrared (NIR) region. However, most of nanocarriers lack target capacity for combining chemotherapy and photothermal therapy effects. Herein, we reported chitosan (CS)-encapsulated and folic acid (FA)-modified nanoparticles (NPs) simultaneously loading with functionalized CuS NCs and docetaxel (DTX) (FA-DTX-PVP/CuS-NPs). Compared with free DTX, the photothermal agent CuS NCs and DTX not only could be specially targeted to deliver into MCF-7 cancer cells via a receptor-mediated endocytosis pathway, but also could be effectively transferred into tumor tissues of S₁₈₀ tumor-bearing mice in vivo. More important, when combination with NIR laser irradiation, FA-DTX-PVP/CuS-NPs showed a higher antitumor efficacy than the individual therapies. Thus, as a remote and noninvasive tumor therapy strategy, these active targeting NPs may provide a great potential for tumor synergistic therapy.     

Synchronous delivery of oxygen and photosensitizer for alleviation of hypoxia tumor microenvironment and dramatically enhanced photodynamic therapy

Photosensitizer, proper laser irradiation, and oxygen are essential components for effective photodynamic therapy (PDT) in clinical cancer therapy. However, native hypoxic tumoral microenvironment is a major barrier hindering photodynamic reactions in vivo. Thus, we have prepared biocompatible liposomes by loading complexes of oxygen-carrier (hemoglobin, Hb) and photosensitizer (indocyanine green, ICG) for enhanced PDT against hypoxic tumor. Ideal oxygen donor Hb, which is an oxygen-carried protein in red blood cells, makes such liposome which provide stable oxygen supply. ICG, as a photosensitizer, could transfer energy from lasers to oxygen to generate cytotoxic reactive oxygen species (ROS) for treatment. The liposomes loading ICG and Hb (LIH) exhibited efficient tumor homing upon intravenous injection. As revealed by T₂-weighted magnetic resonance imaging and immunohistochemical analysis, the intratumoral hypoxia was greatly alleviated, and the level of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in tumor was obviously down-regulated. A weak PDT efficiency was found in cells incubated in simulated hypoxia condition in vitro, while PDT effect was dramatically enhanced in LIH treated hypoxia cells under near-infrared (NIR) laser, which was mainly attributed to massive generation of ROS with sufficient oxygen supply. ROS trigger oxidative damage of tumors and induce complete suppression of tumor growth and 100% survival rate of mice, which were also in good health condition. Our work highlights a liposome-based nanomedicine that could effectively deliver oxygen to tumor and alleviate tumor hypoxia state, inducing greatly improved efficacy compared to conventional cancer PDT and demonstrates the promise of modulating unfavorable tumor microenvironment with nanotechnology to overcome limitations of cancer therapies.     

Enhanced photodynamic therapy/photothermo therapy for nasopharyngeal carcinoma via a tumour microenvironment-responsive self-oxygenated drug delivery system

The hypoxic nature of tumours limits the efficiency of oxygen-dependent photodynamic therapy (PDT). Hence, in this study, indocyanine green (ICG)-loaded lipid-coated zinc peroxide (ZnO₂) nanoparticles (ZnO₂@Lip-ICG) was constructed to realize tumour microenvironment (TME)-responsive self-oxygen supply. Near infrared light irradiation (808 nm), the lipid outer layer of ICG acquires sufficient energy to produce heat, thereby elevating the localised temperature, which results in accelerated ZnO₂ release and apoptosis of tumour cells. The ZnO₂ rapidly generates O₂ in the TME (pH 6.5), which alleviates tumour hypoxia and then enhances the PDT effect of ICG. These results demonstrate that ZnO₂@Lip-ICG NPs display good oxygen self-supported properties and outstanding PDT/PTT characteristics, and thus, achieve good tumour proliferation suppression.     

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.     

Spotlight on the delivery of photosensitizers: different approaches for photodynamic-based therapies

Introduction: Nanomedicine development allowed the discovery of new photosensitizers (PS) and drug delivery systems (DDS) to overcome current issues on phototherapy. Nano-engineered materials have the potential to improve the solubility of PS, control drug pharmacokinetics, decreasing side effects, increasing bioavailability, and overcoming multidrug resistance. A recent approach is the co-delivery of PS with other therapeutic agents in a multimodal platform for synergic and improved results.

Areas covered: This paper discusses the delivery of PS-nanostructured platforms for conventional, photothermal, and antimicrobial photodynamic therapies, as well as in a recent therapeutic modality for photobiomodulation, covering applications of cancer diagnosis, targeting to skin pathogens, photoregeneration and wound healing. The focus of the present review is to describe the use of different DDS to enhance the therapeutic outcomes triggered by the combination of delivered PS, light, and oxygen.

Expert opinion: Nanotechnology allowed the development of site-specific delivery of PS molecules, expanding possibilities poorly explored before to enhance photodynamic efficacy and extrapolate the concept to other treatment protocols. Research in this area embraces potential and pitfalls of PS delivery, allowing new clinical phase outcomes and long-term issues to be established, which will impact on several biomedical applications.     

Sharp pH-sensitive amphiphilic polypeptide macrophotosensitizer for near infrared imaging-guided photodynamic therapy

Tumor environmental sensitive polypeptide integrated photosensitizer is a platform for imaging-guided photodynamic therapy (PDT). However, the photosensitizer leakage during blood circulation, poor accumulation in tumor tissue and inferior quantum yield of singlet oxygen are still challenges. Herein, NHS-active boron-dipyrromethene derivative with bromine substituted NHS-BODIPY-Br₂ was first synthesized, which possessed high singlet oxygen generation efficiency and near infrared (NIR) fluorescence, and then it was conjugated to a sharp pH (6.36) sensitive polypeptide to achieve a macrophotosensitizer for NIR imaging-guided PDT. In vitro study showed that the macrophotosensitizer nanoparticles exhibited good cellular uptake and ability to kill cancer cells. Once accumulating in the tumor tissues, the nanoparticles can be demicellized by tumor acidity to promote cellular uptake, which could enlarge fluorescence signal intensity and enhance in vivo PDT therapeutic effect upon NIR laser irradiation. It provides a strategy to design photosensitizer conjugated tumor acidity sensitive polypeptide for NIR imaging-guided photodynamic therapy.     

Liposomes in topical photodynamic therapy

Introduction: Topical photodynamic therapy (PDT) refers to topical application of a photosensitizer onto the site of skin disease which is followed by illumination and results in death of selected cells. The main problem in topical PDT is insufficient penetration of the photosensitizer into the skin, which limits its use to superficial skin lesions. In order to overcome this problem, recent studies tested liposomes as delivery systems for photosensitizers.

Areas covered: This paper reviews the use of different types of liposomes for encapsulating photosensitizers for topical PDT. Liposomes should enhance the photosensitizers' penetration into the skin, while decreasing its absorption into systemic circulation. Only few photosensitizers have currently been encapsulated in liposomes for topical PDT: 5-aminolevulinic acid (5-ALA), temoporfin (mTHPC) and methylene blue.

Expert opinion: Investigated liposomes enhanced the skin penetration of 5-ALA and mTHPC, reduced their systemic absorption and reduced their cytotoxicity compared with free drugs. Their high tissue penetration should enable the treatment of deep and hyperkeratotic skin lesions, which is the main goal of using liposomes. However, liposomes still do not attract enough attention as drug carriers in topical PDT. In vivo studies of their therapeutic effectiveness are needed in order to obtain enough evidence for their potential clinical use as carriers for photosensitizers in topical PDT.     

Innovative strategies for photodynamic therapy against hypoxic tumor

Photodynamic therapy (PDT) is applied as a robust therapeutic option for tumor, which exhibits some advantages of unique selectivity and irreversible damage to tumor cells. Among which, photosensitizer (PS), appropriate laser irradiation and oxygen (O₂) are three essential components for PDT, but the hypoxic tumor microenvironment (TME) restricts the O₂ supply in tumor tissues. Even worse, tumor metastasis and drug resistance frequently happen under hypoxic condition, which further deteriorate the antitumor effect of PDT. To enhance the PDT efficiency, critical attention has been received by relieving tumor hypoxia, and innovative strategies on this topic continue to emerge. Traditionally, the O₂ supplement strategy is considered as a direct and effective strategy to relieve TME, whereas it is confronted with great challenges for continuous O₂ supply. Recently, O₂-independent PDT provides a brand new strategy to enhance the antitumor efficiency, which can avoid the influence of TME. In addition, PDT can synergize with other antitumor strategies, such as chemotherapy, immunotherapy, photothermal therapy (PTT) and starvation therapy, to remedy the inadequate PDT effect under hypoxia conditions. In this paper, we summarized the latest progresses in the development of innovative strategies to improve PDT efficacy against hypoxic tumor, which were classified into O₂-dependent PDT, O₂-independent PDT and synergistic therapy. Furthermore, the advantages and deficiencies of various strategies were also discussed to envisage the prospects and challenges in future study.     

Incorporation of chemotherapeutic agent and photosensitizer in a low temperature-sensitive liposome for effective chemo-hyperthermic anticancer activity

Objectives: In this study, we combined chemo- and hyperthermia therapy in a low temperature-sensitive liposome (LTSL) for potential cancer treatment.

Methods: Docetaxel (DOC) and indocyanine green (ICG) as a therapeutic agent and photosensitizer, respectively, were incorporated in a low temperature-sensitive liposome (LTSL/DI). Nanoparticles were evaluated for the physicochemical characterizations, in vitro uptake and cytotoxicity, and furthermore in vivo anticancer activity.

Results: The particle size of LTSL/DI was 130.8 ± 2.3 nm, and its drug release profile was pH- and temperature-dependent, which are effective for tumor targeting. The in vitro anticancer activity of LTSL/DI was significantly enhanced compared with free DOC in SCC-7 and MCF-7 cell lines. Interestingly, near-infrared laser irradiation after the treatment resulted in better anticancer activity than in the non-irradiated condition. The in vivo tumor regression effect of LTSL/DI in combination with NIR irradiation was much greater compared with the control group in SCC-7 tumor-bearing mice. After intratumoral injection of LTSL/DI, local heat induced by NIR irradiation and the localized docetaxel burst release could completely ablate the tumor, and inhibit its recurrence.

Conclusions: These results suggest LTSL/DI formulation as a potential therapeutic strategy with effectively localized anti-tumor activity and low risk of side effect to non-target organs.     

Single-walled carbon nanotubes mediated targeted tamoxifen delivery system using aspargine-glycine-arginine peptide

Abstract

An aspargine-glycine-arginine (NGR) peptide modified single-walled carbon nanotubes (SWCNTs) system, developed by a simple non-covalent approach, could be loaded with the anticancer drug tamoxifen (TAM). This TAM-loaded NGR modified SWCNTs (TAM/NGR-SWCNTs) not only retained both optical properties of SWCNTs and cytotoxicity of TAM, but also could accumulate in tumors and enter into 4T1 cells, which facilitated combination chemotherapy with photothermal therapy in one targeting system. Enhanced cellular uptake, antitumor effect and cell apoptosis of TAM/NGR-SWCNTs on 4T1 cells were observed in vitro, compared with the TAM solution, TAM/SWCNTs and photothermal therapy alone. In vivo investigation of TAM/NGR-SWCNTs in tumor-bearing mice further confirmed that this system possessed much higher tumor targeting capacity and antitumor efficacy than the control, especially with the near-infrared-laser irradiation treatment. Moreover, it demonstrated negligible systematic toxicity through the histopathological analysis. All these results suggest TAM/NGR-SWCNTs are promising for high targeted efficiency and treatment efficacy and low side effects of future cancer therapy by synergistic effect of chemo-photothermal combination.     

吲哚菁绿光热治疗耐甲氧西林葡萄球菌感染的研究

目的　探讨吲哚菁绿（ICG）的光热治疗（PTT）性能及对耐甲氧西林葡萄球菌的杀灭效果。方法　利用紫外和荧光光谱对ICG的光物理性质进行表征;测定不同质量浓度ICG（0、12.5、25、50、100和200 mg/L）的光热升温曲线,评估ICG的光热转化性能;取小鼠乳腺癌4T1细胞与不同质量浓度的ICG溶液（0、50、100、200和500 mg/L）混合,通过MTT实验检测ICG的细胞毒性;取1×1010 CFU/mL的耐甲氧西林的金黄色葡萄球菌加入到96孔板中,将实验分为7组：PBS组、ICG组（500 mg/L）、激光照射组（1.5 W/cm2的808 nm激光照射10 min）、ICG+0.33 W/cm2激光照射组、ICG+0.66 W/cm2激光照射组、ICG+1 W/cm2激光照射组、ICG+1.5 W/cm2激光照射组,观察并记录存活的菌落数,分析基于ICG的PTT杀菌效果。结果　紫外吸收光谱证实ICG在808 nm处具有较强的光吸收能力;ICG溶液（质量浓度为200 mg/L）经功率密度为1.5 W/cm2的808 nm近红外激光照射10 min后,温度可升高23.3 ℃,而纯水的温度仅升高了4.8 ℃。ICG不同质量浓度组即50、100、200、500 mg/L组的细胞生存率分别为81.87%±2.69%、81.47%±2.94%、82.92%±2.61%、80.44%±2.98%,组间差异无统计学意义（F=0.402,P＞0.05）。不同功率密度激光照射组即0.33、0.66、1、1.5 W/cm2组的细胞生存率分别为97.21%±1.59%、94.92%±1.98%、93.89%±1.38%、93.03%±2.31%,组间差异无统计学意义（F=2.864,P＞0.05）。杀菌实验中,与PBS组比较,ICG+激光照射组随着激光功率密度的升高,细菌存活数量逐渐下降,差异有统计学意义（F=133.800,P＜0.01）。结论　ICG具有良好的生物相容性和光热治疗性能,在近红外激光照射下对耐甲氧西林葡萄球菌具有较强的杀灭效果,具有较好的临床转化应用价值。     

Tailored core‒shell dual metal–organic frameworks as a versatile nanomotor for effective synergistic antitumor therapy

Malignant tumor has become an urgent threat to global public healthcare. Because of the heterogeneity of tumor, single therapy presents great limitations while synergistic therapy is arousing much attention, which shows desperate need of intelligent carrier for co-delivery. A core‒shell dual metal–organic frameworks (MOFs) system was delicately designed in this study, which not only possessed the unique properties of both materials, but also provided two individual specific functional zones for co-drug delivery. Photosensitizer indocyanine green (ICG) and chemotherapeutic agent doxorubicin (DOX) were stepwisely encapsulated into the nanopores of MIL-88 core and ZIF-8 shell to construct a synergistic photothermal/photodynamic/chemotherapy nanoplatform. Except for efficient drug delivery, the MIL-88 could be functioned as a nanomotor to convert the excessive hydrogen peroxide at tumor microenvironment into adequate oxygen for photodynamic therapy. The DOX release from MIL-88-ICG@ZIF-8-DOX nanoparticles was triggered at tumor acidic microenvironment and further accelerated by near-infrared (NIR) light irradiation. The in vivo antitumor study showed superior synergistic antitumor effect by concentrating the nanoparticles into dissolving microneedles as compared to intravenous and intratumoral injection of nanoparticles, with a significantly higher inhibition rate. It is anticipated that the multi-model synergistic system based on dual-MOFs was promising for further biomedical application.     

Dendrimer and cancer: a patent review (2006 – present)

Introduction: Dendrimers were widely used in cancer diagnosis and therapy during the past decade. The surface functionalities allow bioactive molecules such as imaging probes, therapeutic compounds, targeting ligands to be present on dendrimer surface in a multivalent fashion. In addition, the interior pockets as well as the charged surface of dendrimer can be encapsulated/bound with anti-cancer drugs or therapeutic DNAs/siRNAs.

Areas covered: The combination of dendrimer chemistry and new cancer therapy techniques such as radiotherapy, photodynamic therapy, neuron capture therapy, and photothermal therapy provides promising strategies in future cancer therapy. Here, we focused on recent advances on this topic in the patents (2006 – present) and discussed the advantages of dendrimer technology in these inventions.

Expert opinion: The challenges and perspectives of dendrimer-based theranostics for cancer diagnosis and therapy are discussed. Future efforts in this area should be focused on designing materials to solve problems such as cancer metastasis, multidrug resistance (MDR) in cancer cells, and early-stage cancer diagnosis.     

Recent trends in targeted therapy of cancer using graphene oxide-modified multifunctional nanomedicines

Rapid progresses in nanotechnology fields have led us to use a number of advanced nanomaterials (NMs) for engineering smart multifunctional nanoparticles (NPs)/nanosystems (NSs) for targeted diagnosis and therapy of various diseases including different types of malignancies. For the effective therapy of any type of solid tumor, the treatment modality should ideally solely target the aberrant cancerous cells/tissue with no/trivial impacts on the healthy cells. One approach to achieve such unprecedented impacts can be fulfilled through the use of seamless multimodal NPs/NSs with photoacoustic properties that can be achieved using advanced NMs such as graphene oxide (GO). It is considered as one of the most promising materials that have been used in the development of various NPs/NSs. GO-based targeted NSs can be engineered as programmable drug delivery systems (DDSs) to perform on-demand chemotherapy combined with photonic energy for photothermal therapy (PTT) or photodynamic therapy (PDT). In the current review, we provide important insights on the GO-based NSs and discuss their potentials for the photodynamic/photothermal ablation of cancer in combination with anticancer agents.     

Verteporfin PDT for subfoveal occult CNV in AMD: two-year results of a randomized trial

ABSTRACT

Objective: To determine whether verteporfin photodynamic therapy (PDT) can safely reduce the risk of vision loss in patients with subfoveal occult with no classic choroidal neovascularization (CNV) due to age-related macular degeneration.

Research design and methods: Eligible patients were ≥50 years of age with lesion size ≤6 disc areas and best-corrected vision 20/40–20/200. A total of 364 patients with occult with no classic CNV were randomly assigned 2 : 1 to verteporfin PDT (n?=?244) or placebo (n?=?120). The primary outcome measures were loss of ≥15 and ≥30 letters of visual acuity (VA) from baseline at 12 and 24 months.

Results: A total of 37% and 47% of verteporfin-treated patients versus 45% and 53% of placebo recipients lost ≥15 letters of VA at month 12 and month 24, respectively; 16% and 23% of verteporfin-treated patients versus 17% and 25% of placebo recipients lost ≥30 letters at month 12 and month 24, respectively. These differences were not statistically significant. Four (1.6%) verteporfin-treated patients and one placebo patient (who received verteporfin in error) experienced an acute severe VA decrease; all five patients recovered some degree of vision. No unexpected ocular or systemic adverse events were identified.

Conclusions: Verteporfin PDT in the treatment of occult with no classic CNV was safe and well-tolerated. The differences between the two groups in the primary efficacy variables were not significant. Baseline characteristics and patient selection methods may have contributed to the small treatment effect.

Trial registration: ClinicalTrials.gov identifier: NCT00121407.