Iron oxide@chlorophyll clustered nanoparticles eliminate bladder cancer by photodynamic immunotherapy-initiated ferroptosis and immunostimulation

• Published in: Journal of nanobiotechnology Vol. 20; no. 1; pp. 1 - 18
• Main Authors: Chin, Yu-Cheng, Yang, Li-Xing, Hsu, Fei-Ting, Hsu, Che-Wei, Chang, Te-Wei, Chen, Hsi-Ying, Chen, Linda Yen-Chien, Chia, Zi Chun, Hung, Chun-Hua, Su, Wu-Chou, Chiu, Yi-Chun, Huang, Chih-Chia, Liao, Mei-Yi
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 11.08.2022; BioMed Central; BMC
• Subjects: Anticancer properties; Antitumor activity; Apoptosis; Bladder; Bladder cancer; Cancer; Cancer therapies; Care and treatment; CD8 antigen; Cell death; Chlorophyll; Cytotoxicity; Effectiveness; Effector cells; Efficiency; Ferroptosis; Fluorescence; Glycoproteins; Health aspects; Immune response; Immune system; Immunostimulation; Immunosuppression; Immunosurveillance; Immunotherapy; Iron oxides; Lipid peroxidation; Lipids; Lymphocytes; Lymphocytes T; Macrophages; Nanoparticles; PD-L1 protein; Peroxidation; Photochemotherapy; Photodynamic therapy; Photoinduction; Reactive oxygen species; Singlet oxygen; Survival; Technology application; Therapeutics, Experimental; Toxicity; Tumor microenvironment; Tumors; Taiwan
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/s12951-022-01575-7

The escape of bladder cancer from immunosurveillance causes monotherapy to exhibit poor efficacy; therefore, designing a multifunctional nanoparticle that boosts programmed cell death and immunoactivation has potential as a treatment strategy. Herein, we developed a facile one-pot coprecipitation reaction to fabricate cluster-structured nanoparticles (CNPs) assembled from Fe 3 O 4 and iron chlorophyll (Chl/Fe) photosensitizers. This nanoassembled CNP, as a multifunctional theranostic agent, could perform red-NIR fluorescence and change the redox balance by the photoinduction of reactive oxygen species (ROS) and attenuate iron-mediated lipid peroxidation by the induction of a Fenton-like reaction. The intravesical instillation of Fe 3 O 4 @Chl/Fe CNPs modified with 4-carboxyphenylboronic acid (CPBA) may target the BC wall through glycoproteins in the BC cavity, allowing local killing of cancer cells by photodynamic therapy (PDT)-induced singlet oxygen and causing chemodynamic therapy (CDT)-mediated ferroptosis. An interesting possibility is reprogramming of the tumor microenvironment from immunosuppressive to immunostimulatory after PDT-CDT treatment, which was demonstrated by the reduction of PD-L1 (lower “off” signal to the effector immune cells), IDO-1, TGF-β, and M2-like macrophages and the induction of CD8 +  T cells on BC sections. Moreover, the intravesical instillation of Fe 3 O 4 @Chl/Fe CNPs may enhance the large-area distribution on the BC wall, improving antitumor efficacy and increasing survival rates from 0 to 91.7%. Our theranostic CNPs not only demonstrated combined PDT-CDT-induced cytotoxicity, ROS production, and ferroptosis to facilitate treatment efficacy but also opened up new horizons for eliminating the immunosuppressive effect by simultaneous PDT-CDT.