ATP-exhausted nanocomplexes for intratumoral metabolic intervention and photoimmunotherapy

Yu, Mian; Zeng, Weiwei; Ouyang, Yaqi; Liang, Shu; Yi, Yunfei; Hao, Huisong; Yu, Jiayin; Liu, Yang; Nie, Yichu; Wang, Tianqi; Deng, Yang; Wu, Meiying

doi:10.1016/j.biomaterials.2022.121503

Cited by 27 publications

(23 citation statements)

References 34 publications

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“…Yu et al. 202 constructed an ATP-exhausted nanocomplex by the self-assembly of siRNA/PEI complex, imidazole-2-carboxaldehyde (2-ICA) and Zn 2+ , with electrostatic adsorbed ICG and surface coated RGD-decorated polylactic acid-hyperbranched polyglycerol (PLA-HPG-RGD), which not only intervened in tumor energy metabolism to regulate TME but also depleted excessive intracellular ATP and inhibited ATP synthesis, thereby enhancing PTT-induced ICD. Mao et al.…”

Section: Strategies For Remodeling Immunosuppressive Tmementioning

confidence: 99%

Targeted nanomedicines remodeling immunosuppressive tumor microenvironment for enhanced cancer immunotherapy

Xiong

Sun

et al. 2022

Acta Pharmaceutica Sinica B

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Section: Strategies For Remodeling Immunosuppressive Tmementioning

confidence: 99%

Targeted nanomedicines remodeling immunosuppressive tumor microenvironment for enhanced cancer immunotherapy

Xiong

Sun

et al. 2022

Acta Pharmaceutica Sinica B

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“…For the primary tumor inoculation, 10 6 4T1 cells were injected into the right breast fat pad of female BALB/c mice at day − 7. For the distal tumor inoculation, 5 × 10 5 4T1 cells were injected into the left breast fat pad at day − 3 [7]. After the primary tumor volume reached about 100-200mm 3 , mice were divided into six groups (n = 5): PBS, Rg3@PPP, DOX@PPP, Rg3-PNPs + DOX@ PPP, αPD-L1@PPP (αPD-L1 loaded hydrogel) and (Rg3-PNPs + DOX + αPD-L1)@PPP.…”

Section: Establishment Of the Bilateral 4t1 Tumor Model To Examine Th...mentioning

confidence: 99%

“…The binding of HMGB1 to TLR4 stimulates inflammatory responses [6]. Such vaccine-like effect in situ would provoke adaptive immune responses, facilitating the transition of "cold tumors" into "hot tumors" [7], and finally reshaping the immunosuppressive microenvironment and eradicating cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Ginsenoside Rg3 nanoparticles with permeation enhancing based chitosan derivatives were encapsulated with doxorubicin by thermosensitive hydrogel and anti-cancer evaluation of peritumoral hydrogel injection combined with PD-L1 antibody

Wei

Luo

et al. 2022

Biomater Res

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Background Combination of chemotherapy and immune checkpoint inhibitor therapy has greatly improved the anticancer effect on multiple malignancies. However, the efficiency on triple-negative breast cancer (TNBC) is limited, since most patients bear “cold” tumors with low tumor immunogenicity. Doxorubicin (DOX), one of the most effective chemotherapy agents, can induce immunogenic cell death (ICD) and thus initiating immune response. Methods In this study, to maximize the ICD effect induced by DOX, chitosan and cell-penetrating peptide (R6F3)-modified nanoparticles (PNPs) loaded with ginsenoside Rg3 (Rg3) were fabricated using the self-assembly technique, followed by co-encapsulation with DOX based on thermo-sensitive hydrogel. Orthotopic tumor model and contralateral tumor model were established to observe the antitumor efficacy of the thermo-sensitive hydrogel combined with anti-PD-L1 immunotherapy, besides, the biocompatibility was also evaluated by histopathological. Results Rg3-PNPs strengthened the immunogenic cell death (ICD) effect induced by DOX. Moreover, the hydrogel co-loading Rg3-PNPs and DOX provoked stronger immune response in originally nonimmunogenic 4T1 tumors than DOX monotherapy. Following combination with PD-L1 blocking, substantial antitumor effect was achieved due to the recruitment of memory T cells and the decline of adaptive PD-L1 enrichment. Conclusion The hydrogel encapsulating DOX and highly permeable Rg3-PNPs provided an efficient strategy for remodeling immunosuppressive tumor microenvironment and converting immune “cold” 4T1 into “hot” tumors.

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“…Benefiting from the boom in nanotechnology and nanomedicine in recent decades, numerous noble metal-containing radiosensitizers, like gold-, wolfram (W)-, and bismuth-containing nanomaterials, are exploited to selectively increase radiation energy deposition on tumors to reinforce RT while alleviating unexpected body injury, owing to strong ionizing radiation energy absorption of noble metal. − Compared with inorganic radiosensitizers, organic ones are characterized by simpler preparation, easier surface modification, and better biocompatibility, which guarantees relatively good biosecurity to body and clinical transformation potential in the future. − However, their design and fabrication are fussy and challenging on account of inert characteristic of mostly noble metal, which in general, require high-temperature and high-pressure conditions. On the other hand, improving tumor targeting is also an alternative strategy for amplifying the accumulated difference in radiosensitizers between tumor and normal tissues, thereby strengthening RT with insignificant side effects. − Overall, it is difficult but crucial to develop noble metal-containing organic radiosensitizers with active targeting capability to maximize radiation deposition on the tumor for enhancing RT.…”

Section: Introductionmentioning

confidence: 99%

Targeted Wolfram-Doped Polypyrrole for Photonic Hyperthermia-Synergized Radiotherapy

Wang

Zeng

Liang

et al. 2022

ACS Appl. Mater. Interfaces

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Single ionizing radiation at a tolerable dose is ineffectual in eliminating malignancies but readily generates harmful effects on surrounding normal tissues. Herein, we intelligently fabricated novel wolfram-doped polypyrrole (WPPy) through a simple oxidative polymerization method with WCl 6 as an oxidizing catalyst, which possessed good biocompatibility, high photothermal conversion, and intensive radiosensitivity capacities to concurrently serve as a photothermal reagent and a radiosensitizer for hyperthermia-synergized radiotherapy (RT) against a malignant tumor. In comparison with traditional polypyrrole without noble metal doping, the innovative introduction of WCl 6 not only successfully launched the polymerization of a pyrrole monomer but also endowed WPPy with additional radiosensitization. More importantly, after further decoration with an active targeted component (SP94 polypeptide), the obtained WPPy@SP94 significantly increased tumor internalization and accumulation in vitro and in vivo and induced obvious DNA damage as well as robust ROS generation under X-ray irradiation, which meanwhile synergized with strong photonic hyperthermia to effectively inhibit tumor growth by single drug injection. Moreover, such biocompatible WPPy@SP94 showed negligible adverse effects on normal cells and tissues. WPPy@SP94 developed in this study not only expands the category of polypyrrole chemical syntheses but also sheds light on WPPy@SP94-based radiosensitizers for cancer RT.

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ATP-exhausted nanocomplexes for intratumoral metabolic intervention and photoimmunotherapy

Cited by 27 publications

References 34 publications

Targeted nanomedicines remodeling immunosuppressive tumor microenvironment for enhanced cancer immunotherapy

Targeted nanomedicines remodeling immunosuppressive tumor microenvironment for enhanced cancer immunotherapy

Ginsenoside Rg3 nanoparticles with permeation enhancing based chitosan derivatives were encapsulated with doxorubicin by thermosensitive hydrogel and anti-cancer evaluation of peritumoral hydrogel injection combined with PD-L1 antibody

Targeted Wolfram-Doped Polypyrrole for Photonic Hyperthermia-Synergized Radiotherapy

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