scholarly journals NIR-II-driven and glutathione depletion-enhanced hypoxia-irrelevant free radical nanogenerator for combined cancer therapy

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Li Zhang ◽  
Yadi Fan ◽  
Zhe Yang ◽  
Mo Yang ◽  
Chun-Yuen Wong

Abstract Background Though the combination of photodynamic therapy (PDT) and chemodynamic therapy (CDT) appears to be very attractive in cancer treatment, hypoxia and overproduced glutathione (GSH) in the tumor microenvironment (TME) limit their efficacy for further application. Results In this work, a smart hypoxia-irrelevant free radical nanogenerator (AIPH/PDA@CuS/ZIF-8, denoted as APCZ) was synthesized in situ via coating copper sulphide (CuS)-embedded zeolitic imidazolate framework-8 (ZIF-8) on the free radical initiator 2,2′-azobis[2-(2-imidazolin-2-yl)propane]-dihydrochloride (AIPH)-loaded polydopamine (PDA). APCZ showed promising GSH-depleting ability and near-infrared (NIR)-II photothermal performance for combined cancer therapy. Once internalized by 4T1 cells, the outer ZIF-8 was rapidly degraded to trigger the release of CuS nanoparticles (NPs), which could react with local GSH and sequentially hydrogen peroxide (H2O2) to form hydroxyl radical (·OH) for CDT. More importantly, the hyperthermia generated by APCZ upon 1064 nm laser excitation not only permitted NIR-II photothermal therapy (PTT) and promoted CDT, but also triggered the decomposition of AIPH to give toxic alkyl radical (·R) for oxygen-independent PDT. Besides, the PDA together with CuS greatly decreased the GSH level and resulted in significantly enhanced PDT/CDT in both normoxic and hypoxic conditions. The tumors could be completely eradicated after 14 days of treatment due to the prominent therapeutic effects of PTT/PDT/CDT. Additionally, the feasibility of APCZ as a photoacoustic (PA) imaging contrast agent was also demonstrated. Conclusions The novel APCZ could realize the cooperative amplification effect of free radicals-based therapies by NIR-II light excitation and GSH consumption, and act as a contrast agent to improve PA imaging, holding tremendous potential for efficient diagnosis and treatment of deep-seated and hypoxic tumors. Graphic abstract

Nanoscale ◽  
2021 ◽  
Author(s):  
Weiwei Wu ◽  
Yan Yang ◽  
Zhuoying Liang ◽  
Xiling Song ◽  
Yadong Huang ◽  
...  

Recently, alkyl radical has attracted much attention in cancer therapy due to its oxygen-independent generation property. For the first time, alkyl radical and nitric oxide (NO) combined therapy is demonstrated...


Author(s):  
Feng Wu ◽  
Fei Qiu ◽  
Siew Anthony Wai-Keong ◽  
Yong Diao

Background: In recent years, the emergence of stimuli-responsive nanoparticles makes drug delivery more efficient. As an intelligent and effective targeted delivery platform, it can reduce the side effects generated during drug transportation while enhancing the treatment efficacy. The stimuli-responsive nanoparticles can respond to different stimuli at corresponding times and locations to deliver and release their drugs and associated therapeutic effects. Objective: This review aims to inform researchers on the latest advances in the application of dual-stimuli responsive nanoparticles in precise drug delivery, with special attention to their design, drug release properties, and therapeutic effects. Syntheses of nanoparticles with simultaneous or sequential responses to two or more stimuli (pH-redox, pH-light, redoxlight, temperature-magnetic, pH-redox-temperature, redox-enzyme-light, etc.) and the applications of such responsivity properties for drugs control and release have become a hot topic of recent research. Methods: A database of relevant information for the production of this review was sourced, screened and analyzed from Pubmed, Web of Science, SciFinder by searching for the following keywords: “dual-stimuli responsive”, “controlled release”, “cancer therapy”, “synergistic treatment”. Results: Notably, the nanoparticles with dual-stimuli responsive function have an excellent control effect on drug delivery and release, playing a crucial part in the treatment of tumors. They can improve the encapsulation and delivery efficiency of hydrophobic chemotherapy drugs, combine chemo-photothermal therapies, apply imaging function in the diagnosis of tumors and even conduct multi-drugs delivery to overcome multi-drugs resistance (MDR). Conclusion: With the development of smart dual-stimuli responsive nanoparticles, cancer treatment methods will become more diverse and effective. All the stimuli-responsive nanoparticles functionalities exhibited their characteristics individually within the single nanosystem.


Author(s):  
Xiaowei Luan ◽  
Yongchun Pan ◽  
Yanfeng Gao ◽  
Yujun Song

Light has witnessed the history of mankind and even the universe. It is of great significances to the life of human society, contributing to energy, agriculture, communication, and much more....


Nanoscale ◽  
2021 ◽  
Author(s):  
Jinsong Xiong ◽  
Qinghuan Bian ◽  
Shuijin Lei ◽  
Yatian Deng ◽  
Kehan Zhao ◽  
...  

Near-infrared (NIR) light induced photothermal cancer therapy using nanomaterials as photothermal agents has attracted considerable research interest over the past few years. As the key factor in the photothermal therapy...


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wan Fatin Amira Wan Mohd Zawawi ◽  
M. H. Hibma ◽  
M. I. Salim ◽  
K. Jemon

AbstractBreast cancer is the most common cancer that causes death in women. Conventional therapies, including surgery and chemotherapy, have different therapeutic effects and are commonly associated with risks and side effects. Near infrared radiation is a technique with few side effects that is used for local hyperthermia, typically as an adjuvant to other cancer therapies. The understanding of the use of near NIR as a monotherapy, and its effects on the immune cells activation and infiltration, are limited. In this study, we investigate the effects of HT treatment using NIR on tumor regression and on the immune cells and molecules in breast tumors. Results from this study demonstrated that local HT by NIR at 43 °C reduced tumor progression and significantly increased the median survival of tumor-bearing mice. Immunohistochemical analysis revealed a significant reduction in cells proliferation in treated tumor, which was accompanied by an abundance of heat shock protein 70 (Hsp70). Increased numbers of activated dendritic cells were observed in the draining lymph nodes of the mice, along with infiltration of T cells, NK cells and B cells into the tumor. In contrast, tumor-infiltrated regulatory T cells were largely diminished from the tumor. In addition, higher IFN-γ and IL-2 secretion was observed in tumor of treated mice. Overall, results from this present study extends the understanding of using local HT by NIR to stimulate a favourable immune response against breast cancer.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Ruixue Huang ◽  
Ping-Kun Zhou

AbstractGenomic instability is the hallmark of various cancers with the increasing accumulation of DNA damage. The application of radiotherapy and chemotherapy in cancer treatment is typically based on this property of cancers. However, the adverse effects including normal tissues injury are also accompanied by the radiotherapy and chemotherapy. Targeted cancer therapy has the potential to suppress cancer cells’ DNA damage response through tailoring therapy to cancer patients lacking specific DNA damage response functions. Obviously, understanding the broader role of DNA damage repair in cancers has became a basic and attractive strategy for targeted cancer therapy, in particular, raising novel hypothesis or theory in this field on the basis of previous scientists’ findings would be important for future promising druggable emerging targets. In this review, we first illustrate the timeline steps for the understanding the roles of DNA damage repair in the promotion of cancer and cancer therapy developed, then we summarize the mechanisms regarding DNA damage repair associated with targeted cancer therapy, highlighting the specific proteins behind targeting DNA damage repair that initiate functioning abnormally duo to extrinsic harm by environmental DNA damage factors, also, the DNA damage baseline drift leads to the harmful intrinsic targeted cancer therapy. In addition, clinical therapeutic drugs for DNA damage and repair including therapeutic effects, as well as the strategy and scheme of relative clinical trials were intensive discussed. Based on this background, we suggest two hypotheses, namely “environmental gear selection” to describe DNA damage repair pathway evolution, and “DNA damage baseline drift”, which may play a magnified role in mediating repair during cancer treatment. This two new hypothesis would shed new light on targeted cancer therapy, provide a much better or more comprehensive holistic view and also promote the development of new research direction and new overcoming strategies for patients.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fatemeh Yousefimehr ◽  
Saeed Jafarirad ◽  
Roya Salehi ◽  
Mohammad Sadegh Zakerhamidi

AbstractIn this study, we report a facile green-synthesis route for the fabrication of reduced graphene oxide (rGO) using biomass of Brassica oleracea var. gongylodes (B. oleracea). In addition, we have attempted to provide a green synthesis approach to prepare Gold nanoparticles (Au NPs) on the surface of rGO by using stem extract of B. oleracea. The synthesized Au/rGO nanocomposite was evaluated using UV–visible and FTIR spectroscopy, XRD, Raman, FE-SEM, EDX, AFM and DLS techniques. The obtained results demonstrated that the synthesized Au NPs on the surface of rGO was spherical with sizes ranging about 12–18 nm. The Au/rGO NC was, also, developed as photo-synthesizer system for the photothermal therapy (PTT) of MCF7 breast cancer cells. The near-infrared (NIR) photothermal properties of Au/rGO NCs was evaluated using a continuous laser at 808 nm with power densities of 1 W.cm−2. Their photothermal efficacy on MCF7 breast cancer cells after optimizing the proper concentration of the NCs were evaluated by MTT assay, Cell cycle and DAPI staining. In addition, the potential of the synthesized Au/rGO NCs on reactive oxygen species generating and antioxidant activity were assessed by DPPH. Au/rGO NCs possess high capacity to light-to-heat conversion for absorption in range NIR light, and it is able to therapeutic effects on MCF7 cells at a low concentration. The maximum amount of cell death is 40.12% which was observed in treatment groups that received a combination of Au/rGO NCs and laser irradiation. The results demonstrate that the nanomaterials synthesized by green approach lead to efficient destruction of cancer cell and might thus serve as an excellent theranostic agent in Photothermal therapy applications.


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