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  1. Free, publicly-accessible full text available August 22, 2024
  2. Amphiphilic block copolymer micelles can mimic the ability of natural lung surfactant to reduce the air–water interfacial tension down close to zero and prevent the Laplace pressure-induced alveolar collapse. In this work, we investigated the air–water interfacial behaviors of polymer micelles derived from eight different poly(ethylene glycol)(PEG)-based block copolymers having different hydrophobic block chemistries to elucidate the effect of the core block chemistry on the surface mechanics of the block copolymer micelles. Aqueous micelles of about 30 nm in hydrodynamic diameter were prepared from the PEG-based block copolymers via equilibrium nanoprecipitation and spread on water surface using water as the spreading medium. Surface pressure–area isotherm and quantitative Brewster angle microscopy measurements were performed to investigate how the micelle/monolayer structures change during lateral compression of the monolayer; widely varying structural behaviors were observed, including wrinkling/collapse of micelle monolayers, and deformation and/or desorption of individual micelles. By bivariate correlation regression analysis of surface pressure-area isotherm data, it was found that the rigidity and hydrophobicity of the hydrophobic core domain, which are quantified by glass transition temperature (Tg) and water contact angle (θ) measurements, respectively, are coupled factors that need to be taken into account concurrently in order to control the surface mechanical properties of polymer micelle monolayers; micelles having rigid and strongly hydrophobic cores exhibited high surface pressure and high compressibility modulus under high compression. High surface pressure and high compressibility modulus were also found to be correlated with the formation of wrinkles in the micelle monolayer (visualized by Brewster angle microscopy). From this study, we conclude that polymer micelles based on hydrophobic block materials having higher Tg and θ are more suitable for surfactant replacement therapy applications which require the therapeutic surfactant to produce high surface pressure and modulus at the alveolar air–water interface. 
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  3. Photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) prodrug is a clinically tried and proven treatment modality for surface-level lesions. However, its use for deep-seated tumors has been limited due to the poor penetration depth of visible light needed to activate the photosensitizer protoporphyrin IX (PPIX), which is produced from ALA metabolism. Herein, we report the usage of poly(ethylene glycol- b -lactic acid) (PEG–PLA)-encapsulated calcium tungstate (CaWO 4 , CWO for short) nanoparticles (PEG–PLA/CWO NPs) as energy transducers for X-ray-activated PDT using ALA. Owing to the spectral overlap between radioluminescence afforded by the CWO core and the absorbance of PPIX, these NPs can serve as an in situ visible light activation source during radiotherapy (RT), thereby mitigating the limitation of penetration depth. We demonstrate that this effect is observed across different cell lines with varying radio-sensitivity. Importantly, both PPIX and PEG–PLA/CWO NPs exhibit no significant toxicities at therapeutic doses in the absence of radiation. To assess the efficacy of this approach, we conducted a study using a syngeneic mouse model subcutaneously implanted with inherently radio-resistant 4T1 tumors. The results show a significantly improved prognosis compared to conventional RT, even with as few as 2 fractions of 4 Gy X-rays. Taken together, these results suggest that PEG–PLA/CWO NPs are promising agents for application of ALA-PDT in deep-seated tumors, thereby significantly expanding the utility of the already established treatment strategy. 
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  4. Abstract

    Rare but consistent reports of abscopal remission in patients challenge the notion that radiotherapy (RT) is a local treatment; radiation‐induced cancer cell death can trigger activation and recruitment of dendritic cells to the primary tumor site, which subsequently initiates systemic immune responses against metastatic lesions. Although this abscopal effect was initially considered an anomaly, combining RT with immune checkpoint inhibitor therapies has been shown to greatly improve the incidence of abscopal responses via modulation of the immunosuppressive tumor microenvironment. Preclinical studies have demonstrated that nanomaterials can further improve the reliability and potency of the abscopal effect for various different types of cancer by (1) altering the cell death process to be more immunogenic, (2) facilitating the capture and transfer of tumor antigens from the site of cancer cell death to antigen‐presenting cells, and (3) co‐delivering immune checkpoint inhibitors along with radio‐enhancing agents. Several unanswered questions remain concerning the exact mechanisms of action for nanomaterial‐enhanced RT and for its combination with immune checkpoint inhibition and other immunostimulatory treatments in clinically relevant settings. The purpose of this article is to summarize key recent developments in this field and also highlight knowledge gaps that exist in this field. An improved mechanistic understanding will be critical for clinical translation of nanomaterials for advanced radio‐immunotherapy.

    This article is categorized under:

    Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease

     
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