Mitochondria-Targeting Oxygen-Sufficient Perfluorocarbon Nanoparticles for Imaging-Guided Tumor Phototherapy.

BACKGROUND: Although photothermal therapy (PTT) and photodynamics therapy (PDT) have both made excellent progress in tumor therapy, the effectiveness of using PTT or PDT alone is dissatisfactory due to the limitations of the penetration depth in PTT and the hypoxic microenvironment of tumors for PDT. Combination phototherapy has currently become a burgeoning cancer treatment. METHODS AND MATERIALS: In this work, a mitochondria-targeting liquid perfluorocarbon (PFC)-based oxygen delivery system was developed for the synergistic PDT/photothermal therapy (PTT) of cancer through image guiding. RESULTS: Importantly, these nanoparticles (NPs) can effectively and accurately accumulate in the target tumor via the enhanced permeability and retention (EPR) effect. CONCLUSION: This approach offers a novel technique to achieve outstanding antitumor efficacy by an unprecedented design with tumor mitochondria targeting, oxygen delivery, and synergistic PDT/PTT with dual-imaging guidance.

Near-Infrared Laser-Triggered, Self-Immolative Smart Polymersomes for in vivo Cancer Therapy.

PURPOSE: Traditional chemotherapy is accompanied by significant side effects, which, in many aspects, limits its treatment efficacy and clinical applications. Herein, we report an oxidative responsive polymersome nanosystem mediated by near infrared (NIR) light which exhibited the combination effect of photodynamic therapy (PDT) and chemotherapy. METHODS: In our study, poly (propylene sulfide)20-bl-poly (ethylene glycol)12 (PPS20-b-PEG12) block copolymer was synthesized and employed to prepare the polymersome. The hydrophobic photosensitizer zinc phthalocyanine (ZnPc) was loaded in the shell and the hydrophilic doxorubicin hydrochloride (DOX·HCl) in the inner aqueous space of the polymersome. RESULTS: Under the irradiation of 660 nm NIR light, singlet oxygen 1O2 molecules were generated from ZnPc to oxidize the neighbouring sulfur atoms on the PPS block which eventually ruptured the intact structure of polymersomes, leading to the release of encapsulated DOX·HCl. The released DOX and the 1O2 could achieve a combination effect for cancer therapy if the laser activation and drug release occur at the tumoral sites. In vitro studies confirmed the generation of singlet oxygen and DOX release by NIR irradiation. In vivo studies showed that such a combined PDT-chemotherapy nanosystem could accumulate in A375 tumors efficiently, thus leading to significant inhibition on tumor growth as compared to PDT (PZ group) or chemotherapy alone (DOX group). CONCLUSION: In summary, this oxidation-sensitive nanosystem showed excellent anti-tumor effects by synergistic chemophotodynamic therapy, indicating that this novel drug delivery strategy could potentially provide a new means for cancer treatments in clinic.

Epidermal Growth Factor Receptor-Targeted Delivery of a Singlet-Oxygen Sensitizer with Thermal Controlled Release for Efficient Anticancer Therapy.

Photodynamic therapy (PDT) utilizing light-induced singlet oxygen has achieved attractive results in anticancer fields; however, its development is hindered by limited light penetration depth, skin phototoxicity, tumor hypoxia, and PDT-induced hypoxia. Inspired by our previous research work and the limitations of PDT, we introduce a small-molecule-targeted drug erlotinib into the singlet-oxygen chemical source endoperoxide to achieve an EGFR-targeted PDT-mimetic sensitizer (Y3-1) for anticancer therapy. We demonstrated the erlotinib-based precise delivery of the singlet-oxygen chemical source (in vitro photosensitization) to EFGR-overexpressing tumor cells and tissues. Moreover, the anticancer assays validated that the enhanced anticancer efficacy (in vitro and in vivo) of Y3-1 was due to reversible singlet-oxygen thermal release. This study is expected to provide a smart strategy to break through the current roadblock in targeted PDT and achieve a more efficient anticancer therapy model.

Antibacterial efficacy of photosensitizer functionalized biopolymeric nanoparticles in the presence of tissue inhibitors in root canal.

INTRODUCTION: Application of antibacterial nanoparticles to improve root canal disinfection has received strong interest recently. The current study aims to assess the antibacterial effect of a novel photosensitizer (rose bengal functionalized chitosan nanoparticles [CSRBnp]) to eliminate bacteria in the presence of various root canal constituents that are known to inhibit the antibacterial efficacy of root canal disinfectants. METHODS: The synthesized CSRBnp were evaluated for size, charge, and singlet oxygen release. The antibacterial effect of CSRBnp was tested on planktonic Enterococcus faecalis with or without pretreatment by using different inhibiting agents such as dentin, dentin-matrix, pulp tissue, bacterial lipopolysaccharides, and bovine serum albumin (BSA). Bacterial survival was assessed in a time-dependent manner. The antibacterial effects after photodynamic activation on CSRBnp, a cationic photosensitizer (methylene blue), and an anionic photosensitizer (rose bengal [RB]) in the presence of inhibitors were also evaluated. RESULTS: CSRBnp were 60 ± 20 nm in size and showed reduced rate of singlet oxygen release as compared with methylene blue and RB. Pulp and BSA inhibited the antibacterial effect of CSRBnp (without photoactivation) significantly (P < .05) even after 24 hours of interaction. In case of photodynamic therapy, the pulp and BSA significantly inhibited the antibacterial activity of all 3 photosensitizers. CSRBnp showed residual effect and completely eliminated the bacteria after 24 hours of interaction after photodynamic therapy. CONCLUSIONS: The inherent antibacterial activity of polycationic chitosan nanoparticles and the singlet oxygen released after photoactivation of RB synergistically provided CSRBnp the potential to achieve significant antibacterial efficacy even in the presence of tissue inhibitors within root canals.