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| 1 | A Review on Nano-Based Drug Delivery System for Cancer Chemoimmunotherapy显示文摘Although notable progress has been made on novel cancer treatments,the overall survival rate and therapeutic effects are still unsatisfactory for cancer patients.Chemoimmunotherapy,combining chemotherapeutics and immunotherapeutic drugs,has emerged as a promising approach for cancer treatment,with the advantages of cooperating two kinds of treatment mechanism,reducing the dosage of the drug and enhancing therapeutic effect.Moreover,nano-based drug delivery system(NDDS)was applied to encapsulate chemotherapeutic agents and exhibited outstanding properties such as targeted delivery,tumor microenvironment response and site-specific release.Several nanocarriers have been approved in clinical cancer chemotherapy and showed significant improvement in therapeutic efficiency compared with traditional formulations,such as liposomes(Doxil R,Lipusu R),nanoparticles(Abraxane R)and micelles(Genexol-PM R).The applications of NDDS to chemoimmunotherapy would be a powerful strategy for future cancer treatment,which could greatly enhance the therapeutic efficacy,reduce the side effects and optimize the clinical outcomes of cancer patients.Herein,the current approaches of cancer immunotherapy and chemoimmunotherapy were discussed,and recent advances of NDDS applied for chemoimmunotherapy were further reviewed. | Weiwei Mu Qihui Chu Yongjun Liu Na Zhang | 2020 | Nano-Micro Letters2020，12，10： | 8 |
| 2 | Abrogation of USP7 is an alternative strategy to downregulate PD-L1 and sensitize gastric cancer cells to T cells killing显示文摘Targeting immune checkpoints such as programmed cell death protein 1(PD-1)and programmed death ligand-1(PD-L1)have been approved for treating melanoma,gastric cancer(GC)and bladder cancer with clinical benefit.Nevertheless,many patients failed to respond to anti-PD-1/PD-L1 treatment,so it is necessary to seek an alternative strategy for traditional PD-1/PD-L1 targeting immunotherapy.Here with the data from The Cancer Genome Atlas(TCGA)and our in-house tissue library,PD-L1 expression was found to be positively correlated with the expression of ubiquitin-specific processing protease 7(USP7)in GC.Furthermore,USP7 directly interacted with PD-L1 in order to stabilize it,Gastric cancer;Immunosuppression;Cancer biologywhile abrogation of USP7 attenuated PD-L1/PD-1 interaction and sensitized cancer cells to T cell killing in vitro and in vivo.Besides,USP7 inhibitor suppressed GC cells proliferation by stabilizing P53 in vitro and in vivo.Collectively,our findings indicate that in addition to inhibiting cancer cells proliferation,USP7 inhibitor can also downregulate PD-L1 expression to enhance anti-tumor immune response simultaneously.Hence,these data posit USP7 inhibitor as an anti-proliferation agent as well as a novel therapeutic agent in PD-L1/PD-1 blockade strategy that can promote the immune response of the tumor. | Zhiru Wang Wenting Kang Ouwen Li Fengyu Qi Junwei Wang Yinghua You Pengxing He Zhenhe Suo Yichao Zheng Hong-Min Liu | 2021 | Acta Pharmaceutica Sinica B2021，11，3： | 5 |
| 3 | Polysaccharide-based nanomedicines for cancer immunotherapy:A review显示文摘Cancer immunotherapy is an effective antitumor approach through activating immune systems to eradicate tumors by immunotherapeutics.However,direct administration of“naked”immunotherapeutic agents(such as nucleic acids,cytokines,adjuvants or antigens without delivery vehicles)often results in:(1)an unsatisfactory efficacy due to suboptimal pharmacokinetics;(2)strong toxic and side effects due to low targeting(or off-target)efficiency.To overcome these shortcomings,a series of polysaccharide-based nanoparticles have been developed to carry immunotherapeutics to enhance antitumor immune responses with reduced toxicity and side effects.Polysaccharides are a family of natural polymers that hold unique physicochemical and biological properties,as they could interact with immune system to stimulate an enhanced immune response.Their structures offer versatility in synthesizing multifunctional nanocomposites,which could be chemically modified to achieve high stability and bioavailability for delivering therapeutics into tumor tissues.This review aims to highlight recent advances in polysaccharide-based nanomedicines for cancer immunotherapy and propose new perspectives on the use of polysaccharide-based immunotherapeutics. | Yujun Zeng Yufan Xiang Ruilong Sheng Helena Tomás João Rodrigues Zhongwei Gu Hu Zhang Qiyong Gong Kui Luo | 2021 | Bioactive Materials2021，6，10： | 3 |
| 4 | Hyperthermia based individual in situ recombinant vaccine enhances lymph nodes drainage for de novo antitumor immunity显示文摘The continuing challenges that limit effectiveness of tumor therapeutic vaccines were high heterogeneity of tumor immunogenicity, low bioactivity of antigens, as well as insufficient lymph nodes(LNs) drainage of antigens and adjuvants. Transportation of in situ neoantigens and adjuvants to LNs may be an effective approach to solve the abovementioned problems. Therefore, an FA-TSL/AuNCs/SV nanoplatform was constructed by integrating simvastatin(SV) adjuvant loaded Au nanocages(AuNCs)as cores(AuNCs/SV) and folic acid modified thermal-sensitive liposomes(FA-TSL) as shells to enhance de novo antitumor immunity. After accumulation in tumor guided by FA, AuNCs mediated photothermal therapy(PTT) induced the release of tumor-derived protein antigens(TDPAs) and the shedding of FATSL. Exposed AuNCs/SV soon captured TDPAs to form in situ recombinant vaccine(AuNCs/SV/TDPAs). Subsequently, AuNCs/SV/TDPAs could efficiently transport to draining LNs owing to the hyperthermia induced vasodilation effect and small particle size, achieving co-delivery of antigens and adjuvant for initiation of specific T cell response. In melanoma bearing mice, FA-TSL/AuNCs/SV and laser irradiation effectively ablated primary tumor, against metastatic tumors and induced immunological memory. This approach served a hyperthermia enhanced platform drainage to enable robust personalized cancer vaccination. | Cuixia Zheng Xinxin Liu Yueyue Kong Lei Zhang Qingling Song Hongjuan Zhao Lu Han Jiannan Jiao Qianhua Feng Lei Wang | 2022 | Acta Pharmaceutica Sinica B2022，12，8： | 2 |
| 5 | Combining immune checkpoint blockade with ATP-based immunogenic cell death amplifier for cancer chemo-immunotherapy显示文摘Amplifying“eat me signal”during tumor immunogenic cell death(ICD)cascade is crucial for tumor immunotherapy.Inspired by the indispensable role of adenosine triphosphate(ATP,a necessary“eat me signal”for ICD),a versatile ICD amplifier was developed for chemotherapy-sensitized immunotherapy.Doxorubicin(DOX),ATP and ferrous ions(Fe^(2+))were co-assembled into nanosized amplifier(ADO-Fe)throughπ‒πstacking and coordination effect.Meanwhile,phenylboric acid-polyethylene glycol-phenylboric acid(PBA-PEG-PBA)was modified on the surface of ADO-Fe(denoted as PADO-Fe)by the virtue of d-ribose unit of ATP.PADO-Fe could display active targetability against tumor cells via sialic acid/PBA interaction.In acidic microenvironment,PBA-PEG-PBA would dissociate from amplifier.Moreover,high H_(2)O_(2)concentration would induce hydroxyl radical(·OH)and oxygen(O_(2))generation through Fenton reaction by Fe^(2+).DOX and ATP would be released from the amplifier,which could induce ICD effect and“ICD adjuvant”to amplify this process.Together with programmed death ligands 1(PD-L1)checkpoint blockade immunotherapy,PADO-Fe could not only activate immune response against primary tumor,but also strong abscopal effect against distant tumor.Our simple and multifunctional ICD amplifier opens a new window for enhancing ICD effect and immune checkpoint blockade therapy. | Jiulong Zhang Xiaoyan Sun Xiufeng Zhao Chunrong Yang Menghao Shi Benzhuo Zhang Haiyang Hu Mingxi Qiao Dawei Chen Xiuli Zhao | 2022 | Acta Pharmaceutica Sinica B2022，12，9： | 2 |
| 6 | Lenvatinib-and vadimezan-loaded synthetic high-density lipoprotein for combinational immunochemotherapy of metastatic triple-negative breast cancer显示文摘Metastatic triple-negative breast cancer(TNBC)is the most aggressive type of breast cancer.Combination of systemic chemotherapy and immune checkpoint blockade is effective but of limited benefit due to insufficient intratumoral infiltration of cytotoxic T lymphocytes(CTLs)and the accumulation of immunosuppressive cells.Herein,we designed a lenvatinib-and vadimezan-loaded synthetic high-density lipoprotein(LV-sHDL)for combinational immunochemotherapy of metastatic TNBC.The LV-sHDL targeted scavenger receptor class B type 1-overexpressing 4T1 cells in the tumor after intravenous injection.The multitargeted tyrosine kinase inhibitor(TKI)lenvatinib induced immunogenic cell death of the cancer cells,and the stimulator of interferon genes(STING)agonist vadimezan triggered local inflammation to facilitate dendritic cell maturation and antitumor macrophage differentiation,which synergistically improved the intratumoral infiltration of total and active CTLs by 33-and 13-fold,respectively.LV-sHDL inhibited the growth of orthotopic 4T1 tumors,reduced pulmonary metastasis,and prolonged the survival of animals.The efficacy could be further improved when LV-sHDL was used in combination with antibody against programmed cell death ligand 1.This study highlights the combination use of multitargeted TKI and STING agonist a promising treatment for metastatic TNBC. | Chao Zheng Wen Zhang Jinming Wang Yihui Zha Fengqin Xiong Ying Cai Xiang Gong Binyu Zhu Helen He Zhu Hao Wang Yaping Li Pengcheng Zhang | 2022 | Acta Pharmaceutica Sinica B2022，12，9： | 1 |
| 7 | Anti-PD-L1 mediating tumor-targeted codelivery of liposomal irinotecan/JQ1 for chemo-immunotherapy显示文摘Immune checkpoint blockade therapy has become a first-line treatment in various cancers.But there are only a small percent of colorectal patients responding to PD-1/PD-L1 blockage immunotherapy.How to increase their treatment efficacy is an urgent and clinically unmet need.It is acknowledged that immunogenic cell death(ICD)induced by some specific chemotherapy can enhance antitumor immunity.Chemo-based combination therapy can yield improved outcomes by activating the immune system to eliminate the tumor,compared with monotherapy.Here,we develop a PD-L1-targeting immune liposome(P-Lipo)for co-delivering irinotecan(IRI)and JQ1,and this system can successfully elicit antitumor immunity in colorectal cancer through inducing ICD by IRI and interfering in the immunosuppressive PD-1/PD-L1 pathway by JQ1.P-Lipo increases intratumoral drug accumulation and promotes DC maturation,and thereby facilitates adaptive immune responses against tumor growth.The remodeling tumor immune microenvironment was reflected by the increased amount of CD8+T cells and the release of IFN-γ,and the reduced CD4+Foxp3+regulatory T cells(Tregs).Collectively,the P-Lipo codelivery system provides a chemo-immunotherapy strategy that can effectively remodel the tumor immune microenvironment and activate the host immune system and arrest tumor growth. | Zhi-di He Meng Zhang Yong-hui Wang Yang He Hai-rui Wang Bin-fan Chen Bin Tu Si-qi Zhu Yong-zhuo Huang | 2021 | Acta Pharmacologica Sinica2021，42，9： | 0 |
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