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NIR Activated Multimodal Therapeutics Based on Metal-Phenolic Networks-Functionalized Nanoplatform for Combating
Chen Cheng1,2, Weixi Jiang1, Yuanli Luo1
1Department of Ultrasound and Chongqing Key Laboratory of Ultrasound Molecular Imaging, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, P. R. China.
Abstract:
Multidrug resistance (MDR) and metastasis in cancer have become increasingly serious problems since antitumor efficiency is greatly restricted by a single therapeutic modality and the insensitive tumor microenvironment (TME). Herein, metal-phenolic network-functionalized nanoparticles (t-P@TFP NPs) are designed to realize multiple therapeutic modalities and reshape the TME from insensitive to sensitive under multimodal imaging monitoring. After a single irradiation, a near-infrared laser-activated multistage reaction occurs. t-P@TFP NPs trigger the phase transition of perfluoropentane (PFP) to release tannic acid (TA)/ferric ion (Fe3+ )-coated paclitaxel (PTX) and cause hyperthermia in the tumor region to efficiently kill cancer cells. Additionally, PTX is released after the disassembly of the TA-Fe3+ film by the abundant adenosine triphosphate (ATP) in the malignant tumor, which concurrently inhibits ATP-dependent drug efflux to improve sensitivity to chemotherapeutic agents. Furthermore, hyperthermia-induced immunogenic cell death (ICD) transforms "cold" tumors into "hot" tumors with the assistance of PD-1/PD-L1 blockade to evoke antitumor immunogenicity. This work carefully reveals the mechanisms underlying the abilities of these multifunctional NPs, providing new insights into combating the proliferation and metastasis of multidrug-resistant tumors.
Insights
Multidrug-resistant (MDR) cancer and metastasis are combated by novel nanoparticles. These nanoparticles deliver chemotherapy, induce hyperthermia, and enhance immunotherapy by reprogramming the tumor microenvironment (TME).
Area of Science:
- Biomaterials Science
- Nanotechnology
- Cancer Therapy
Background:
- Multidrug resistance (MDR) and cancer metastasis limit current therapeutic efficacy.
- The tumor microenvironment (TME) is often insensitive to single-modality treatments.
Purpose of the Study:
- To develop multifunctional nanoparticles (t-P@TFP NPs) for multimodal cancer therapy.
- To reshape the TME from insensitive to sensitive under multimodal imaging guidance.
- To overcome MDR and metastasis in tumors.
Main Methods:
- Design and synthesis of metal-phenolic network-functionalized nanoparticles (t-P@TFP NPs).
- NIR laser-triggered multistage reactions including perfluoropentane (PFP) phase transition and drug release.
- Hyperthermia induction and chemotherapy (paclitaxel, PTX) delivery.
- Adenosine triphosphate (ATP)-mediated drug release and inhibition of drug efflux.
- Combination therapy with PD-1/PD-L1 blockade for immunotherapy.
Main Results:
- t-P@TFP NPs effectively kill cancer cells via hyperthermia and chemotherapy.
- ATP-sensitive drug release and enhanced chemosensitivity were achieved.
- Hyperthermia induced immunogenic cell death (ICD), converting 'cold' tumors to 'hot' tumors.
- Multimodal imaging monitoring guided the therapeutic process.
Conclusions:
- The developed t-P@TFP NPs offer a promising strategy for combating MDR and metastatic cancers.
- This approach enhances antitumor efficacy by combining chemotherapy, hyperthermia, and immunotherapy.
- Reshaping the TME and overcoming drug resistance are key benefits of this nanoplatform.
