Enzyme-triggered size shrink and laser-enhanced NO release nanoparticles for deep tumor penetration and combination therapy

Hu, Chuan; Cun, Xingli; Ruan, Shaobo; Li, Rui; Xiao, Wei; Yang, Xiaotong; Yang, Yuanyuan; Yang, Chuanyao; Gao, Huile

doi:10.1016/j.biomaterials.2018.03.046

Cited by 250 publications

(144 citation statements)

References 64 publications

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“…Distribution in Tumor Spheroids : According to method reported previously, low‐melting point agarose dissolved in cell culture medium (2%, w/v) was added into 96‐well plates (80 µL per well) and placed to gelate. 4T1 cells were seeded on gel (3 × 10 3 cells per well) and allowed to form spheroids.…”

Section: Methodsmentioning

confidence: 99%

Linear Chimeric Triblock Molecules Self‐Assembled Micelles with Controllably Transformable Property to Enhance Tumor Retention for Chemo‐Photodynamic Therapy of Breast Cancer

Yang

et al. 2019

Adv Funct Materials

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Although nanoparticles are expected to revolutionize cancer treatment, their low efficacy remains the greatest limiting factor. Recent investigations found that nanoparticles' golden principle, the enhanced permeability and retention (EPR) effect, is limited by the complicated tumor microenvironment. Herein, novel transformable nanomaterials are designed to utilize the EPR effect more effectively. By tandem conjugation of the hydrophobic head (chlorin e6 (Ce6) or bilirubin (BR)), peptide to form hydrogen bond (Phe-Phe-Val-Leu-Lys (FFVLK)), and hydrophilic tail (polyethylene glycol (PEG)), chimeric molecules that can form micelles (Ce6/BR-FFVLK-PEG) in aqueous solution are synthesized. Notably, the spherical micelles retain shape transformability. After circulation and distribution, they respond to 650 nm laser irradiation, and morphologically change into nanofibers so as to facilitate their retention markedly inside the tumor. Upon loading a reactive oxygen species-responsive paclitaxel dimer with thioketal linker (PTX 2 -TK), the resultant PTX 2 -TK@Ce6/BR-FFVLK-PEG nanomedicine serves as a potent chemo-photodynamic therapeutic for cancer treatment. Evaluations at both cell level and animal level reveal that PTX 2 -TK@Ce6/BR-FFVLK-PEG exhibits superior biocompatibility and biodistribution, and suppresses 82.6% of in vitro cell growth and 61.8% of in vivo tumor growth at a common dose of intravenous injection (10 mg kg −1 PTX and 3.3 mg kg −1 Ce6), becoming a novel nanomedicine with extraordinary potential in cancer therapy.

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Section: Methodsmentioning

confidence: 99%

Linear Chimeric Triblock Molecules Self‐Assembled Micelles with Controllably Transformable Property to Enhance Tumor Retention for Chemo‐Photodynamic Therapy of Breast Cancer

Yang

et al. 2019

Adv Funct Materials

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“…Mountains of NDDSs rely on the enhanced permeability and retention (EPR) effect to passively target tumor tissue . Nevertheless, their tumor accumulations remain low and need improvement.…”

Section: Introductionmentioning

confidence: 99%

Tumor Microenvironment‐Responsive Dual Drug Dimer‐Loaded PEGylated Bilirubin Nanoparticles for Improved Drug Delivery and Enhanced Immune‐Chemotherapy of Breast Cancer

Yang

Tong

et al. 2019

Adv Funct Materials

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104

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The application of combinational therapy makes up for the limitation of monotherapy and achieves superior treatment against cancer. However, the combinational therapy remains restricted by the poor tumor-specific delivery and the abscopal effect. Herein, reactive oxygen species (ROS)responsive PEGylated bilirubin nanoparticles (BRNPs) are developed to encapsulate two glutathione-activatable drugs, including dimer-7ethyl-10-hydroxycamptothecin (d-SN38) and dimer-lonidamine (d-LND). Dimerization of the drugs significantly increases the drug loading capacity and the encapsulation efficiency of nanoparticles. With the assistance of iRGD peptide (cRGDKGPDC), the cellular uptake of BRNPs is more than double when compared with the control. In response to high levels of intracellular ROS, d-SN38 and d-LND are rapidly released from nanoparticles (SL@BRNPs). Furthermore, the pharmacodynamic experiments verify combining SL@BRNPs with anti-PD-L1 antibody greatly inhibits the primary tumor of breast cancer, improves CD8+ T cells levels, and CD8+ T cells/Tregs ratios in the tumor. Additionally, it shows high immune memory effect and can prevent the growth of lung metastasis. Taken together, the strategy pioneers a new way for the rational design of nanoassemblies through the combination of activatable drug dimers and stimuli-responsive drug release, and a successful application of novel drug delivery systems in combination with the immune checkpoint blockade antibody.

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“…It is well‐known that disulfide bonds are sensitive to GSH. GSH can induce the rapid cleavage of disulfide bonds, leading to cytosolic delivery of anti‐cancer agents (Y. Cao et al, ; H. Cao et al, ; R. Cheng et al, ; D. Hu et al, ; C. Hu, Cun, et al, ; C. Hu, Fan, et al, ; F. Yu et al, ). A GSH stimuli‐responsive nanomedicine was synthesized by a hydrophobic gramicidin A and a hydrophilic peptide of histidines.…”

Section: Chemical‐responsive Nanomedicinementioning

confidence: 99%

“…So, relevant orthotopic animal models should be established to evaluate the smart nanosystem from the bench to clinics. (Reprinted with permission from C. Hu, Cun, et al (2018). Copyright 2018 Elsevier) Thirdly, the responsive smart nanomedicine has not been evaluated for their long-term systemic toxicity and final clearance routes from animals.…”

Section: Perspectivementioning

confidence: 99%

Physical‐, chemical‐, and biological‐responsive nanomedicine for cancer therapy

Liao

Jia

et al. 2019

WIREs Nanomed Nanobiotechnol

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Cancer therapy is unsatisfactory as it typically has serious side effects, because normal cells in healthy organs are destroyed along with the tumor. Thus, researchers have tried to develop effective therapies with minimal side effects. One such method is to use nanotechnology to carry the drugs or therapeutic agents to the tumor region by secure encapsulation without leakage. Once the nanomedicine enters the target tumor site, it can release therapeutic agents in an effective manner. Accordingly, various nanomedicines have been developed to enhance the efficiency of cancer therapy and minimize the systematic toxicity. Here, we provide an overview and discuss the different types of responsive nanomedicines including physically, chemically, biologically, dual, and multi‐responsive nanomedicines, for the in situ release of cargos in recent years. We propose critical considerations that must be considered for the design of excellent stimuli‐nanomedicine. Furthermore, the possible directions for the development of successful stimuli‐responsive (smart) nanomedicine are highlighted. With the development of responsive nanomedicines, precise and personalized nanomedicine will be realized with great promise in the future. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology

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Enzyme-triggered size shrink and laser-enhanced NO release nanoparticles for deep tumor penetration and combination therapy

Cited by 250 publications

References 64 publications

Linear Chimeric Triblock Molecules Self‐Assembled Micelles with Controllably Transformable Property to Enhance Tumor Retention for Chemo‐Photodynamic Therapy of Breast Cancer

Linear Chimeric Triblock Molecules Self‐Assembled Micelles with Controllably Transformable Property to Enhance Tumor Retention for Chemo‐Photodynamic Therapy of Breast Cancer

Tumor Microenvironment‐Responsive Dual Drug Dimer‐Loaded PEGylated Bilirubin Nanoparticles for Improved Drug Delivery and Enhanced Immune‐Chemotherapy of Breast Cancer

Physical‐, chemical‐, and biological‐responsive nanomedicine for cancer therapy

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