Study On Phototherapy Of Tumors By Functionalized Black Phosphorus Nanocomposites

Cancer is a refractory disease worldwide,and effective treatment of cancer has always been an important research direction in the field of life sciences.However,traditional cancer treatment methods have shortcomings such as low targeting and high toxic side effects.Photothermal therapy(PTT)and photodynamic therapy(PDT)are considered alternative techniques in clinical cancer treatment due to their advantages of precise spatial localization,minimally invasive and radiation-free manipulation.However,most phototherapeutic agents still suffer from low photothermal conversion efficacy and low photodynamic performance.Black phosphorus nanosheets(BPNS)have broad absorption spectrum,high photothermal conversion efficiency,large specific surface area,and extremely low cytotoxicity,and have been developed for novel biomedical nanomaterials.In addition,BPNS has good biocompatibility,large specific surface area,and extremely low cytotoxicity,and has been developed for novel biomedical nanomaterials.However,the current practical application of BPNS still faces some problems:for example,the hypoxic environment in the tumor microenvironment will sufficiently reduce the PDT effect of the photosensitizer BPNS,the BPNS is easily degraded and loses its activity in the physiological environment,and the BPNS lacks the targeting of precise delivery.Therefore,focusing on how to solve the bottleneck problem of BPNS in tumor phototherapy,two functionalized black phosphorus nanocomposites were proposed in this paper to explore their application in tumor phototherapy.(1)The construction of biocompatible and target-deliverable PTT-PDT self-synergetic nanoplatform of RGD-BPNS@SMFN based on temperature-dependent catalase(CAT)-like behavior for tumor elimination.The homogeneously dispersible nanoplatform is designed and fabricated through anchoring spherical manganese ferrite nanoparticles(SMFN)to black phosphorus nanosheets(BPNS),followed by arginineglycine-aspartic acid(RGD)peptide modification.Compared with common BPNS and SMFN,the nanoplatform exhibited excellent targeting ability and excellent lightresponsive performance both in vitro and in vivo.It is found that PTT and PDT have a self-synergetic behavior by means of the dual phototherapy mode interaction.The selfsynergetic mechanism is mainly ascribed to PTT-promoted inherent CAT-like activity in the nanoplatform,which remodels the tumor hypoxia microenvironment and further ameliorates the PDT efficiency,providing promising high performance nanoplatform for synergetic dual mode phototherapy,enriching the design for the anti-tumor nanozyme.(2)Chirality is ubiquitous in biological systems and is closely linked to the maintenance of organisms and their physiological processes.BPNS exhibit significant in-plane anisotropy,tending to form specific chiral nanostructures.Therefore,it is very meaningful to explore the effect of chirality on the function of BPNS in biological systems.We fabricated chiral BPNS via cysteine modification,and further investigated into the chirality associating tumor phototherapy outcomes.It is inspiring to find although chiral BPNS displayed few differences on the photo-responsiveness in vitro solution environment,PDT and PTT performance on cell and tumor-bearing mice revealed the significant chirality dependence.Specifically,D-Cys-BPNS displayed approximately 3-fold cytotoxic effect on tumor cells in vitro compared to L-form,which is ascribed to its higher intracellular content.This metabolism discrepancy manifested D-form BPNS experience the longer cell membrane adhesion and cytoplasmic decomposition cycle plausibly owing to the L-chirality preference for these behaviors.It is conceivable that chiral engineered BPNS strategy opens new avenue for tuning the phototherapy performance of nanoagent and boosts the chiral nanomedicine development.