Recent Advances in Nanomaterial‐Based Nanoplatforms for Chemodynamic Cancer Therapy

Chemodynamic therapy (CDT), a novel cancer therapeutic strategy defined as the treatment using Fenton or Fenton-like reaction to produce •OH in the tumor region, was first proposed by Bu, Shi, and co-workers in 2016. Recently, with the rapid development of Fenton and Fenton-like nanomaterials, CDT has attracted tremendous attention because of its unique advantages: 1) It is tumor-selective with low side effects; 2) the CDT process does not depend on external field stimulation; 3) it can modulate the hypoxic and immunosuppressive tumor microenvironment; 4) the treatment cost of CDT is low. In addition to the Fe-involved CDT strategies, the Fenton-like reaction-mediated CDT strategies have also been proposed, which are based on many other metal elements including copper, manganese, cobalt, titanium, vanadium, palladium, silver, molybdenum, ruthenium, tungsten, cerium, and zinc. Moreover, CDT has been combined with other therapies like chemotherapy, radiotherapy, phototherapy, sonodynamic therapy, and immunotherapy for achieving enhanced anticancer effects. Besides, there have also been studies that extend the application of CDT to the antibacterial field. This review introduces the latest advancements in the nanomaterials-involved CDT from 2018 to the present and proposes the current limitations as well as future research directions in the related field.

Chemodynamic Therapy via Fenton and Fenton-Like Nanomaterials: Strategies and Recent Advances.

Recent advances in enhanced chemodynamic therapy strategies

The rapid knowledge growth of nanomedicine and nanobiotechnology enables and promotes the emergence of distinctive disease-specific therapeutic modalities, among which nanomedicine-enabled/augmented nanodynamic therapy (NDT), as triggered by either exogenous or endogenous activators on nanosensitizers, can generate reactive radicals for accomplishing efficient disease nanotherapies with mitigated side effects and endowed disease specificity As one of the most representative modalities of NDT, traditional light-activated photodynamics suffers from the critical and unsurmountable issues of the low tissue-penetration depth of light and the phototoxicity of the photosensitizers To overcome these obstacles, versatile nanomedicine-enabled/augmented NDTs have been explored for satisfying varied biomedical applications, which strongly depend on the physicochemical properties of the involved nanomedicines and nanosensitizers These distinctive NDTs refer to sonodynamic therapy (SDT), thermodynamic therapy (TDT), electrodynamic therapy (EDT), piezoelectric dynamic therapy (PZDT), pyroelectric dynamic therapy (PEDT), radiodynamic therapy (RDT), and chemodynamic therapy (CDT) Herein, the critical roles, functions, and biological effects of nanomedicine (eg, sonosensitizing, photothermal-converting, electronic, piezoelectric, pyroelectric, radiation-sensitizing, and catalytic properties) for enabling the therapeutic procedure of NDTs, are highlighted and discussed, along with the underlying therapeutic principle and optimization strategy for augmenting disease-therapeutic efficacy and biosafety The present challenges and critical issues on the clinical translations of NDTs are also discussed and clarified

Emerging Nanomedicine-Enabled/Enhanced Nanodynamic Therapies beyond Traditional Photodynamics.

Janus nanoparticles (JNPs) refer to the integration of two or more chemically discrepant composites into one structure system. Studies into JNPs have been of significant interest due to their interesting characteristics stemming from their asymmetric structures, which can integrate different functional properties and perform more synergetic functions simultaneously. Herein, we present recent progress of Janus particles, comprehensively detailing fabrication strategies and applications. First, the classification of JNPs is divided into three blocks, consisting of polymeric composites, inorganic composites, and hybrid polymeric/inorganic JNPs composites. Then, the fabrication strategies are alternately summarized, examining self-assembly strategy, phase separation strategy, seed-mediated polymerization, microfluidic preparation strategy, nucleation growth methods, and masking methods. Finally, various intriguing applications of JNPs are presented, including solid surfactants agents, micro/nanomotors, and biomedical applications such as biosensing, controlled drug delivery, bioimaging, cancer therapy, and combined theranostics. Furthermore, challenges and future works in this field are provided.

Janus Nanoparticles: From Fabrication to (Bio)Applications.

Photothermal conversion-coordinated Fenton-like and photocatalytic reactions of Cu2-xSe-Au Janus nanoparticles for tri-combination antitumor therapy

http://www.cell.com/article/S096289242200174X/pdf

Calcium homeostasis and cancer: insights from endoplasmic reticulum-centered organelle communications.

Significance Accumulating preclinical and clinical evidence has supported a central role for alterations in Ca2+ homeostasis in the development of cancer. TMCO1 protein is an identified Ca2+-channel protein, while its roles in cancer remain obscure. Here, we found that TMCO1 is increased in colon cancer tissues. In addition, it is a substrate of E3 ligase Gp78. Enhanced oncogene iASPP stabilizes TMCO1 by competitively binding with Gp78. Inhibition of iASPP-TMCO1 sensitizes cancer cells’ response to Ca2+-induced apoptosis. This study has improved our fundamental understanding of the Ca2+ homeostasis in cancer cells. iASPP-TMCO1 axis may present a promising therapeutic target that can combine the conventional drugs to reinforce Ca2+-dependent apoptosis. Ca2+ release from the endoplasmic reticulum (ER) is an essential event in the modulation of Ca2+ homeostasis, which is coordinated by multiple biological processes, ranging from cell proliferation to apoptosis. Deregulated Ca2+ homeostasis is linked with various cancer hallmarks; thus, uncovering the mechanisms underlying Ca2+ homeostasis dynamics may lead to new anticancer treatment strategies. Here, we demonstrate that a reported Ca2+-channel protein TMCO1 (transmembrane and coiled-coil domains 1) is overexpressed in colon cancer tissues at protein levels but not at messenger RNA levels in colon cancer. Further study revealed that TMCO1 is a substrate of ER-associated degradation E3 ligase Gp78. Intriguingly, Gp78-mediated TMCO1 degradation at K186 is under the control of the iASPP (inhibitor of apoptosis-stimulating protein of p53) oncogene. Mechanistically, iASPP robustly reduces ER Ca2+ stores, mainly by competitively binding with Gp78 and interfering with Gp78-mediated TMCO1 degradation. A positive correlation between iASPP and TMCO1 proteins is further validated in human colon tissues. Inhibition of iASPP-TMCO1 axis promotes cytosolic Ca2+ overload–induced apoptotic cell death, reducing tumor growth both in vitro and in vivo. Thus, iASPP-TMCO1 represents a promising anticancer treatment target by modulating Ca2+ homeostasis.

iASPP suppresses Gp78-mediated TMCO1 degradation to maintain Ca2+ homeostasis and control tumor growth and drug resistance

iASPP is essential for HIF-1α stabilization to promote angiogenesis and glycolysis via attenuating VHL-mediated protein degradation

http://www.cell.com/article/S1525001622000144/pdf

Shanliang Zheng

Papers

Photothermal conversion-coordinated Fenton-like and photocatalytic reactions of Cu2-xSe-Au Janus nanoparticles for tri-combination antitumor therapy

Calcium homeostasis and cancer: insights from endoplasmic reticulum-centered organelle communications.

iASPP suppresses Gp78-mediated TMCO1 degradation to maintain Ca2+ homeostasis and control tumor growth and drug resistance

iASPP is essential for HIF-1α stabilization to promote angiogenesis and glycolysis via attenuating VHL-mediated protein degradation

lncRNA HITT inhibits metastasis by attenuating Rab5-mediated endocytosis in lung adenocarcinoma