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Journal ArticleDOI: 10.1021/ACSNANO.0C08996

Precise Depletion of Tumor Seed and Growing Soil with Shrinkable Nanocarrier for Potentiated Cancer Chemoimmunotherapy.

02 Mar 2021-ACS Nano (American Chemical Society (ACS))-Vol. 15, Iss: 3, pp 4636-4646
Abstract: Simultaneously targeting tumor cells and nonmalignant cells represent a more efficient strategy for replacing the traditional method of targeting only tumor cells, and co-delivery nanocarriers have inherent advantages to achieve this goal. However, differential delivery of multiple agents to various types of cell with different spatial distribution patterns remains a large challenge. Herein, we developed a nanocarrier of platinum(IV) prodrug and BLZ-945, BLZ@S-NP/Pt, to differentially target tumor cells and tumor-associated macrophages (TAMs). The BLZ@S-NP/Pt undergoes shrinkage to small platinum(IV) prodrug-conjugating nanoparticles under 660 nm light, resulting in deep tumor penetration to kill more cancer cells. Meanwhile, such shrinkage also enables the rapid release of BLZ-945 in the perivascular regions of tumor to preferentially deplete TAMs (enriched in perivascular regions). Therefore, BLZ@S-NP/Pt differentially and precisely delivers agents to TAMs and tumor cells located in different spatial distribution, respectively, eventually having synergistic anticancer effects in multiple tumor models.

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Topics: Cancer cell (51%), Nanocarriers (51%)
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Journal ArticleDOI: 10.1021/ACSNANO.1C02103
Shan Gao1, Xiaoye Yang1, Jiangkang Xu1, Na Qiu1  +1 moreInstitutions (1)
02 Aug 2021-ACS Nano
Abstract: Immunotherapy that harnesses the human immune system to fight cancer has received widespread attention and become a mainstream strategy for cancer treatment. Cancer immunotherapy not only eliminates primary tumors but also treats metastasis and recurrence, representing a major advantage over traditional cancer treatments. Recently with the development of nanotechnology, there exists much work applying nanomaterials to cancer immunotherapy on the basis of their excellent physiochemical properties, such as efficient tissue-specific delivery function, huge specific surface area, and controllable surface chemistry. Consequently, nanotechnology holds significant potential in improving the efficacy of cancer immunotherapy. Nanotechnology-based immunotherapy mainly manifests its inhibitory effect on tumors via two different approaches: one is to produce an effective anti-tumor immune response during tumorigenesis, and the other is to enhance tumor immune defense ability by modulating the immune suppression mechanism in the tumor microenvironment. With the success of tumor immunotherapy, understanding the interaction between the immune system and smart nanomedicine has provided vigorous vitality for the development of cancer treatment. This review highlights the application, progress, and prospect of nanomedicine in the process of tumor immunoediting and also discusses several engineering methods to improve the efficiency of tumor treatment.

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Topics: Cancer immunotherapy (56%), Immunotherapy (54%), Cancer (54%) ... read more

2 Citations


Journal ArticleDOI: 10.1002/ADTP.202100130
Qinghao Zhou1, Yuheng Wang1, Xiang Li1, Nannan Lu1  +1 moreInstitutions (1)
07 Sep 2021-
Abstract: Stimulator of interferon genes (STING) activation by STING agonists has been recognized as one of important immunotherapy strategies. However, immunosuppressive tumor microenvironment always hinders the therapeutic efficacy of cancer immunotherapy. Herein, ferrocene-containing polymersome nanoreactors are engineered by co-loading glucose oxidase (GOD) and STING agonist, symmetry-linked amidobenzimidazole (DiABZI), for enhanced STING activation and combination chemodynamic-immunotherapy. After intravenous injection, the polymersomes can accumulate in tumor tissues. The tumor acidity-triggered polymersome membrane permeability allows the entrance of tumoral glucose and oxygen for H2O2 production by GOD, which is further transformed into hydroxyl radicals (•OH) under the catalysis of ferrocene moieties. Chemodynamic therapy (CDT) based on •OH can induce efficient cellular apoptosis and release of fragmented DNA and tumor-associated antigens to promote endogenous STING activation and reverse immunosuppressive tumor microenvironment. Simultaneously, pH-responsive release of DiABZI activates STING pathway to elicit antitumor immune responses. Therefore, DiABZI and CDT synergistically enhance the antitumor immunity via combination chemodynamic-immunotherapy. The primary tumors are completely ablated and the growth of distant tumors that are established after treatment is also suppressed efficiently. The polymersome nanoreactor-mediated chemodynamic-immunotherapy represents a promising treatment strategy toward primary solid and metastatic tumors.

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Topics: Polymersome (52%)

1 Citations



Journal ArticleDOI: 10.1016/J.CEJ.2021.132898
Xin Huang1, Ke Ren2, Zhiyong Chang3, Youqing Ye1  +7 moreInstitutions (5)
Abstract: Glioblastoma (GBM) is the most common type of primary malignant brain tumor with few innovative therapies. Developing an efficient and “green” synergistic anticancer strategy for GBM treatment remains a pressing need. Herein, a novel strategy that combines photothermal therapy (PTT), tumor starvation and nitric oxide (NO) therapy based on functionalized black phosphorus nanosheets (BP) is developed. NO-functionalized BP (BPA) is prepared by esterification reaction between the carboxyl group of L-arginine (Arg) and the hydroxyl group (P-OH) formed from the preliminary oxidation on the surface of BP. Then glucose oxidase (GOx) is further introduced to Arg by amidation to form a multimodal nanodrug (BPAG). The mild chemical modification empowers BP with superior stability under physiological condition and induce release of H2O2 and NO by the cascaded oxidation of glucose and Arg. This process can be significantly accelerated by PTT. To facilitate BPAG with tumor-targeting ability, the macrophage membrane is used to coat the nanoparticles under ultrasonic condition. The membrane-coated BPAG (M@BPAG) improves penetration through blood–brain barrier for GBM targeting. Taken together, M@BPAG combines GBM targeting, H2O2-NO release, and PTT effect, leading to reprogramming the tumor immune microenvironment and a significant synergistic antitumor performance without systemic toxicity.

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Journal ArticleDOI: 10.1007/S12274-021-3781-5
Siyuan Chen1, Furong Qin1, Manni Wang1, Yuquan Wei1  +2 moreInstitutions (1)
23 Sep 2021-Nano Research
Abstract: The immunosuppressive tumor microenvironment (TME) is crucial in the occurrence of tumorigenesis, metastasis, and drug resistance. Among all stromal cells, tumor-associated macrophages (TAMs) are recognized as vital components causing the TME to be favorable for cancer cells and are also main targets in cancer immunotherapy. To date, nanoparticle (NP)-based drug delivery systems, as new technology platforms, have exhibited considerable advantages, such as targeted drug delivery at tumor sites, enhanced drug transport efficiency, and controllable drug release profiles, which provide new approaches for cancer therapy. Regarding TAM-targeting nanoparticles, various therapeutic strategies have been developed by varying their design, namely, by blocking TAM recruitment, promoting TAM transformation, and directly diminishing existing TAMs. In the current review, we provide a brief overview of the role of TAMs in the tumor microenvironment and their functions and highlight strategies for TAM targeting. Moreover, the applications of nanoparticles in targeting TAMs to improve cancer therapeutic efficiency are summarized.

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Topics: Targeted drug delivery (57%), Tumor microenvironment (53%), Drug delivery (52%) ... read more
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39 results found


Open accessJournal ArticleDOI: 10.3322/CAAC.21492
Abstract: This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions There will be an estimated 181 million new cancer cases (170 million excluding nonmelanoma skin cancer) and 96 million cancer deaths (95 million excluding nonmelanoma skin cancer) in 2018 In both sexes combined, lung cancer is the most commonly diagnosed cancer (116% of the total cases) and the leading cause of cancer death (184% of the total cancer deaths), closely followed by female breast cancer (116%), prostate cancer (71%), and colorectal cancer (61%) for incidence and colorectal cancer (92%), stomach cancer (82%), and liver cancer (82%) for mortality Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality) Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts CA: A Cancer Journal for Clinicians 2018;0:1-31 © 2018 American Cancer Society

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Topics: Cancer registry (78%), Cancer (72%), Breast cancer (63%) ... read more

39,828 Citations


Open accessJournal ArticleDOI: 10.1038/NM.3394
Daniela F. Quail1, Johanna A. Joyce1Institutions (1)
01 Nov 2013-Nature Medicine
Abstract: Cancers develop in complex tissue environments, which they depend on for sustained growth, invasion and metastasis. Unlike tumor cells, stromal cell types within the tumor microenvironment (TME) are genetically stable and thus represent an attractive therapeutic target with reduced risk of resistance and tumor recurrence. However, specifically disrupting the pro-tumorigenic TME is a challenging undertaking, as the TME has diverse capacities to induce both beneficial and adverse consequences for tumorigenesis. Furthermore, many studies have shown that the microenvironment is capable of normalizing tumor cells, suggesting that re-education of stromal cells, rather than targeted ablation per se, may be an effective strategy for treating cancer. Here we discuss the paradoxical roles of the TME during specific stages of cancer progression and metastasis, as well as recent therapeutic attempts to re-educate stromal cells within the TME to have anti-tumorigenic effects.

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Topics: Tumor progression (58%), Tumor microenvironment (56%), Stromal cell (55%) ... read more

3,971 Citations


Open accessJournal ArticleDOI: 10.1038/NRC2618
Johanna A. Joyce1, Jeffrey W. Pollard2Institutions (2)
Abstract: Metastasis is a multistage process that requires cancer cells to escape from the primary tumour, survive in the circulation, seed at distant sites and grow. Each of these processes involves rate-limiting steps that are influenced by non-malignant cells of the tumour microenvironment. Many of these cells are derived from the bone marrow, particularly the myeloid lineage, and are recruited by cancer cells to enhance their survival, growth, invasion and dissemination. This Review describes experimental data demonstrating the role of the microenvironment in metastasis, identifies areas for future research and suggests possible new therapeutic avenues.

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Topics: Cancer cell (55%), Metastasis (54%), Stromal cell (51%) ... read more

3,044 Citations


Journal ArticleDOI: 10.1038/NRD1033
Abstract: Protein and peptide drugs hold great promise as therapeutic agents. However, many are degraded by proteolytic enzymes, can be rapidly cleared by the kidneys, generate neutralizing antibodies and have a short circulating half-life. Pegylation, the process by which polyethylene glycol chains are attached to protein and peptide drugs, can overcome these and other shortcomings. By increasing the molecular mass of proteins and peptides and shielding them from proteolytic enzymes, pegylation improves pharmacokinetics. This article will review how PEGylation can result in drugs that are often more effective and safer, and which show improved patient convenience and compliance.

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Topics: PEGylation (68%), Proteolytic enzymes (59%)

2,875 Citations


Open accessJournal ArticleDOI: 10.1038/NRC.2016.108
Abstract: The intrinsic limits of conventional cancer therapies prompted the development and application of various nanotechnologies for more effective and safer cancer treatment, herein referred to as cancer nanomedicine. Considerable technological success has been achieved in this field, but the main obstacles to nanomedicine becoming a new paradigm in cancer therapy stem from the complexities and heterogeneity of tumour biology, an incomplete understanding of nano-bio interactions and the challenges regarding chemistry, manufacturing and controls required for clinical translation and commercialization. This Review highlights the progress, challenges and opportunities in cancer nanomedicine and discusses novel engineering approaches that capitalize on our growing understanding of tumour biology and nano-bio interactions to develop more effective nanotherapeutics for cancer patients.

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2,699 Citations