Sonodynamic therapy(SDT)has aroused considerable momentum in cancer therapy due to its abilities of deep penetration,low toxicity,and noninvasion,while insufficient tumor accumulation of sonosensitizers is a major obs...Sonodynamic therapy(SDT)has aroused considerable momentum in cancer therapy due to its abilities of deep penetration,low toxicity,and noninvasion,while insufficient tumor accumulation of sonosensitizers is a major obstacle for SDT effect.Here,we developed a 4T1 cancer cell-macrophage hybrid membrane(HM)-camouflaged sonosensitizer nanoplatform by encapsulating photochlor(HPPH)-loaded albumin nanoparticles(PHNPs).The experimental results proved that the HM-coated biomimetic NPs(PHNPs@HM)could express the characteristic membrane proteins of both cancer cells and macrophages,remarkedly enhancing the effective targeting and endocytosis to 4T1 cells through homologous adhesion recognition and immune escaping.Meanwhile,as a novel sonosensitizer,HPPH could generate amount of reactive oxygen species(ROS)under ultrasound(US)irradiation and exhibit obvious SDT efficiency to inhibit 4T1 tumor growth through ROS-induced cell apoptosis.This study provides a novel and multifunctional biomimetic sonosensitizer system to enhance SDT efficiency.展开更多
Tumor metabolite regulation is intricately linked to cancer progression.Because lactate is a characteristic metabolite of the tumor microenvironment(TME),it supports tumor progression and drives immunosuppression.In t...Tumor metabolite regulation is intricately linked to cancer progression.Because lactate is a characteristic metabolite of the tumor microenvironment(TME),it supports tumor progression and drives immunosuppression.In this study,we presented a strategy for antitumor therapy by developing a nanogold-engineered Rhodospirillum rubrum(R.r-Au)that consumed lactate and produced hydrogen for optical biotherapy.We leveraged a cryogenic micromolding approach to construct a transdermal therapeutic cryomicroneedles(CryoMNs)patch integrated with R.r-Au to efficiently deliver living bacterial drugs.Our long-term storage studies revealed that the viability of R.r-Au in CryoMNs remained above 90%.We found that the CryoMNs patch was mechanically strong and could be inserted into mouse skin.In addition,it rapidly dissolved after administering bacterial drugs and did not produce by-products.Under laser irradiation,R.r-Au effectively enhanced electron transfer through Au NPs actuation into the photosynthetic system of R.rubrum and enlarged lactate consumption and hydrogen production,thus leading to an improved tumor immune activation.Our study demonstrated the potential of CryoMNs-R.r-Au patch as a minimally invasive in situ delivery approach for living bacterial drugs.This research opens up new avenues for nanoengineering bacteria to transform tumor metabolites into effective substances for tumor optical biotherapy.展开更多
基金This work was supported by the National Natural Science Foundation of China(Nos.81901864,81971749,and 82072064)the Natural Science Foundation of Guangdong Province(Nos.2021A1515010131 and 2019A1515011524)+5 种基金Guangdong Province Universities and Colleges Pearl River Scholar Fund(No.4SG21006G)Shenzhen Science and Technology Program(Nos.JCYJ20170818162259843 and JCYJ20210324115607020)Guangdong Province Universities and Colleges Characteristic Innovation(Nos.2021KTSCX035 and 2021KTSCX036)Special Funds of Scientific Technological Innovation of Undergraduates in Guangdong Province(Nos.pdjh2020b0260 and pdjh2020b0265)Guangdong Medical University PHD Funds(2021),Medical Scientific Research Foundation of Guangdong Province(No.A2021429)Zhuhai Innovation and Entrepreneurship Team Project(No.ZH01110405180056PWC).
文摘Sonodynamic therapy(SDT)has aroused considerable momentum in cancer therapy due to its abilities of deep penetration,low toxicity,and noninvasion,while insufficient tumor accumulation of sonosensitizers is a major obstacle for SDT effect.Here,we developed a 4T1 cancer cell-macrophage hybrid membrane(HM)-camouflaged sonosensitizer nanoplatform by encapsulating photochlor(HPPH)-loaded albumin nanoparticles(PHNPs).The experimental results proved that the HM-coated biomimetic NPs(PHNPs@HM)could express the characteristic membrane proteins of both cancer cells and macrophages,remarkedly enhancing the effective targeting and endocytosis to 4T1 cells through homologous adhesion recognition and immune escaping.Meanwhile,as a novel sonosensitizer,HPPH could generate amount of reactive oxygen species(ROS)under ultrasound(US)irradiation and exhibit obvious SDT efficiency to inhibit 4T1 tumor growth through ROS-induced cell apoptosis.This study provides a novel and multifunctional biomimetic sonosensitizer system to enhance SDT efficiency.
基金supported by the National Key Research and Development Program of China (2023YFA0915400,2022YFC2402400)Guangdong Provincial Key Area R&D Program (2020B1111540001)+8 种基金National Natural Science Foundation of China (82303768,82302374)Guangdong Province Universities and Colleges Characteristic Innovation (2021KTSCX036)Traditional Chinese Medicine Research Project of Guangdong Province Traditional Chinese Medicine Bureau (20221206)Shenzhen Medical Research Fund (A2303057)the Natural Science Foundation of Guangdong Province (2022A1515010780,2022A1515011337)the Shenzhen Science and Technology Program (JCYJ20210324101807020,JCYJ20200109114616534)Guangdong Basic and Applied Basic Research Foundation (2022A1515111168)Discipline Construction Project of Guangdong Medical University (4SG24015G)Funds for PHD researchers of Guangdong Medical University in 2024.
文摘Tumor metabolite regulation is intricately linked to cancer progression.Because lactate is a characteristic metabolite of the tumor microenvironment(TME),it supports tumor progression and drives immunosuppression.In this study,we presented a strategy for antitumor therapy by developing a nanogold-engineered Rhodospirillum rubrum(R.r-Au)that consumed lactate and produced hydrogen for optical biotherapy.We leveraged a cryogenic micromolding approach to construct a transdermal therapeutic cryomicroneedles(CryoMNs)patch integrated with R.r-Au to efficiently deliver living bacterial drugs.Our long-term storage studies revealed that the viability of R.r-Au in CryoMNs remained above 90%.We found that the CryoMNs patch was mechanically strong and could be inserted into mouse skin.In addition,it rapidly dissolved after administering bacterial drugs and did not produce by-products.Under laser irradiation,R.r-Au effectively enhanced electron transfer through Au NPs actuation into the photosynthetic system of R.rubrum and enlarged lactate consumption and hydrogen production,thus leading to an improved tumor immune activation.Our study demonstrated the potential of CryoMNs-R.r-Au patch as a minimally invasive in situ delivery approach for living bacterial drugs.This research opens up new avenues for nanoengineering bacteria to transform tumor metabolites into effective substances for tumor optical biotherapy.
