Polymer chimera of stapled oncolytic peptide coupled with anti-PD-L1 peptide boosts immunotherapy of colorectal cancer.

Rationale: Scarce tumor mutation burden and neoantigens create tremendous obstacles for an effective immunotherapy of colorectal cancer (CRC). Oncolytic peptides rise as a promising therapeutic approach that boosts tumor-specific immune responses by inducing antigenic substances. However, the clinical application of oncolytic peptides has been hindered because of structural instability, proteolytic degradation, and undesired toxicity when administered systemically. Methods: Based on wasp venom peptide, an optimized stapled oncolytic peptide MP9 was developed with rigid α-helix, protease-resistance, and CRC cell cytotoxicity. By incorporating four functional motifs that include D-peptidomimetic inhibitor of PD-L1, matrix metalloproteinase-2 (MMP-2) cleavable spacer, and MP9 with 4-arm PEG, a novel peptide-polymer conjugate (PEG-MP9-aPDL1) was obtained and identified as the most promising systemic delivery vehicle with PD-L1 targeting specificity and favorable pharmacokinetic properties. Results: We demonstrated that PEG-MP9-aPDL1-driven oncolysis induces a panel of immunogenic cell death (ICD)-relevant damage-associated molecular patterns (DAMPs) both in vitro and in vivo, which are key elements for immunotherapy with PD-L1 inhibitor. Further, PEG-MP9-aPDL1 exhibited prominent immunotherapeutic efficacy in a CRC mouse model characterized by tumor infiltration of CD8+ T cells and induction of cytotoxic lymphocytes (CTLs) in the spleens. Conclusion: Our findings suggest that PEG-MP9-aPDL1 is an all-in-one platform for oncolytic immunotherapy and immune checkpoint blockade (ICB).

Microfibers: a preliminary discussion on their definition and sources.

Microfibers are a major component of microplastics and have been found nearly everywhere, especially in marine and freshwater habitats around the world. Therefore, microfibers have gained considerable attention in environmental science research. However, there is still no clear consensus on a definition that can encompass all necessary properties to describe microfibers as emerging pollutants. Therefore, we propose a definition for debate by taking the related descriptions of microplastics and textile fibers as references. Moreover, the potential sources from the perspectives of textile engineering, including production, use, care, and end-of-life disposal of fibrous materials, are discussed. For further investigation of microfiber pollution, the gap between current knowledge and major microfiber pollution concerns must be bridged.

Photodynamic Therapy Induced Enhancement of Tumor Vasculature Permeability Using an Upconversion Nanoconstruct for Improved Intratumoral Nanoparticle Delivery in Deep Tissues.

Photodynamic therapy (PDT) has recently emerged as an approach to enhance intratumoral accumulation of nanoparticles. However, conventional PDT is greatly limited by the inability of the excitation light to sufficiently penetrate tissue, rendering PDT ineffective in the relatively deep tumors. To address this limitation, we developed a novel PDT platform and reported for the first time the effect of deep-tissue PDT on nanoparticle uptake in tumors. This platform employed c(RGDyK)-conjugated upconversion nanoparticles (UCNPs), which facilitate active targeting of the nanoconstruct to tumor vasculature and achieve the deep-tissue photosensitizer activation by NIR light irradiation. Results indicated that our PDT system efficiently enhanced intratumoral uptake of different nanoparticles in a deep-seated tumor model. The optimal light dose for deep-tissue PDT (34 mW/cm(2)) was determined and the most robust permeability enhancement was achieved by administering the nanoparticles within 15 minutes following PDT treatment. Further, a two-step treatment strategy was developed and validated featuring the capability of improving the therapeutic efficacy of Doxil while simultaneously reducing its cardiotoxicity. This two-step treatment resulted in a tumor inhibition rate of 79% compared with 56% after Doxil treatment alone. These findings provide evidence in support of the clinical application of deep-tissue PDT for enhanced nano-drug delivery.

Highly efficient ablation of metastatic breast cancer using ammonium-tungsten-bronze nanocube as a novel 1064 nm-laser-driven photothermal agent.

Photothermal ablation (PTA) therapy has been viewed as an invasive option for cancer therapy with minimal deconstruction of healthy tissues. In this study, a potent candidate of (NH4)xWO3 nanocube was developed for PTA treatment of metastatic breast cancer in the second near-infrared (NIR) window. It was found that the as-synthesized (NH4)xWO3 nanocube had significant photoabsorption across the whole NIR window of 780-2500 nm and exhibited considerable photo-heat conversion efficiency. Moreover, the as-prepared (NH4)xWO3 nanocube displayed good biocompatibility and high cellular uptake efficiency through endocytosis pathway without nuclei entry. The PTA study employing 1064 nm laser in the second NIR window revealed that (NH4)xWO3 nanocubes induced significant cell necrosis and apoptosis by producing obviously hyperthermia effect inside cancer cells. Using an orthotopicly implanted breast tumor model, it demonstrated that the (NH4)xWO3 nanocube was a promising photothermal agent for effective ablation of solid tumors and suppressing their distant metastasis.