Tumor microenvironment remodeling-based penetration strategies to amplify nanodrug accessibility to tumor parenchyma

Liu, Yanhong; Zhou, Jiyuan; Li, Qiang; Li, Lingchao; Jia, Yue; Geng, Feiyang; Yin, Tingjie

doi:10.1016/j.addr.2021.02.019

Cited by 59 publications

(40 citation statements)

References 221 publications

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“…Solid tumors, unlike hematologic cancers, have a structure similar to normal tissue, including the parenchyma, which contains neoplastic cells and the surrounding stroma [ 25 , 26 ]. The stroma of solid tumors is critical for cancer cell survival and metabolism through extracellular matrix components and blood vessels [ 27 , 28 ].…”

Section: Effective Vascular Structures For Epr In Solid Tumorsmentioning

confidence: 99%

“…The structural complexities of solid tumors that affect drug delivery pathways remain unclear [ 15 ]. As such, the blood flow complexities mentioned in Section 2 , such as obstruction of fluid flow in the deeper parts of the tumor, tumor heterogeneity due to different types of vessels that cause interstitial fluid pressure, diversity of ECM of solid tumors, and lack of lymphatic drainage vessels, have caused a variety of therapeutic challenges based on the intratumoral transport and drug efficacy [ 20 , 25 , 48 ]. Regardless of the method and location of the injection, the drug nanocarriers introduced in vivo are distributed intratumorally using two basic concepts.…”

Section: Epr-mediated Drug Delivery To Solid Tumorsmentioning

confidence: 99%

See 1 more Smart Citation

An Updated Review on EPR-Based Solid Tumor Targeting Nanocarriers for Cancer Treatment

Sharifi

Cho

Ansariesfahani

et al. 2022

Cancers

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The enhanced permeability and retention (EPR) effect in cancer treatment is one of the key mechanisms that enables drug accumulation at the tumor site. However, despite a plethora of virus/inorganic/organic-based nanocarriers designed to rely on the EPR effect to effectively target tumors, most have failed in the clinic. It seems that the non-compliance of research activities with clinical trials, goals unrelated to the EPR effect, and lack of awareness of the impact of solid tumor structure and interactions on the performance of drug nanocarriers have intensified this dissatisfaction. As such, the asymmetric growth and structural complexity of solid tumors, physicochemical properties of drug nanocarriers, EPR analytical combination tools, and EPR description goals should be considered to improve EPR-based cancer therapeutics. This review provides valuable insights into the limitations of the EPR effect in therapeutic efficacy and reports crucial perspectives on how the EPR effect can be modulated to improve the therapeutic effects of nanomedicine.

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Section: Effective Vascular Structures For Epr In Solid Tumorsmentioning

confidence: 99%

Section: Epr-mediated Drug Delivery To Solid Tumorsmentioning

confidence: 99%

An Updated Review on EPR-Based Solid Tumor Targeting Nanocarriers for Cancer Treatment

Sharifi

Cho

Ansariesfahani

et al. 2022

Cancers

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“…The tumor microenvironment (TME) consists of abnormal tumor vasculature, extracellular matrix components, endothelial cells, pericytes, tumor-associated fibroblasts, smooth muscle cells, and immune cells. Furthermore, the TME plays a crucial role in tumorigenesis, growth, and metastasis ( 22 , 23 ). We used the R package “ESTIMATE” to calculate the stromal score, immune score, ESTIMATEScore, and tumor purity of tumor tissues.…”

Section: Resultsmentioning

confidence: 99%

Clinical Implications of Necroptosis Genes Expression for Cancer Immunity and Prognosis: A Pan-Cancer Analysis

Su²,

Chen³

et al. 2022

Front. Immunol.

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BackgroundNecroptosis, a form of programmed cell death, is increasingly being investigated for its controversial role in tumorigenesis and progression. Necroptosis suppresses tumor formation and tumor development by killing tumor cells; however, the necrotic cells also promote tumor formation and tumor development via the immunosuppressive effect of necroptosis and inflammatory response caused by cytokine release. Thus, the exact mechanism of necroptosis in pan-cancer remains unknown.MethodsThe data of 11,057 cancer samples were downloaded from the TCGA database, along with clinical information, tumor mutation burden, and microsatellite instability information of the corresponding patients. We used the TCGA data in a pan-cancer analysis to identify differences in mRNA level as well as single nucleotide variants, copy number variants, methylation profiles, and genomic signatures of miRNA-mRNA interactions. Two drug datasets (from GDSC, CTRP) were used to evaluate drug sensitivity and resistance against necroptosis genes.ResultsNecroptosis genes were aberrantly expressed in various cancers. The frequency of necroptosis gene mutations was highest in lung squamous cell carcinoma. Furthermore, the correlation between necroptosis gene expression in the tumor microenvironment and immune cell infiltration varied for different cancers. High necroptosis gene expression was found to correlate with NK, Tfh, Th1, CD8_T, and DC cells. These can therefore be used as biomarkers to predict prognosis. By matching gene targets with drugs, we identified potential candidate drugs.ConclusionOur study showed the genomic alterations and clinical features of necroptosis genes in 33 cancers. This may help clarify the link between necroptosis and tumorigenesis. Our findings may also provide new approaches for the clinical treatment of cancer.

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“…Early studies of the immunosuppressive environment identified that extracellular lactate supports the generation of suppressive macrophages and regulatory T cells [ 13 , 14 ]. Further, lactate secretion is proton-coupled, leading to extracellular acidosis suppressing effector reduction [ 15 ]. Recent reports have highlighted that PPAR signaling activated by endogenous fatty acids contributed to immunosuppression in the TME [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Effection of Lactic Acid Dissociation on Swelling-Based Short-Chain Fatty Acid Vesicles Nano-Delivery

Chen

Zhao

Xue

et al. 2022

Foods

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Functionalized small-molecule assemblies can exhibit nano-delivery properties that significantly improve the bioavailability of bioactive molecules. This study explored the self-assembly of short-chain fatty acids (FA, Cn < 8) to form novel biomimetic nanovesicles as delivery systems. Lactic acid is involved in the regulation of multiple signaling pathways in cancer metabolism, and the dissociation of lactic acid (LA) is used to regulate the delivery effect of short-chain fatty acid vesicles. The study showed that the dissociation of lactic acid caused pH changes in the solution environment inducing hydrogen ion permeability leading to rapid osmotic expansion and shape transformation of FA vesicles. The intrinsic features of FA vesicle formation in the LA environment accompanied by hydrogen ion fluctuations, and the appearance of nearly spherical vesicles were investigated by transmission electron microscopy (TEM) and Fourier Transform Infrared Spectroscopy (FTIR). Compared with the vesicle membrane built by surfactants, the FA/LA composite system showed higher permeability and led to better membrane stability and rigidity. Finally, membrane potential studies with the IEC cell model demonstrate that lactate dissociation capacity can effectively increase the cellular adsorption of FA vesicles. Altogether, these results prove that FA vesicles can function as a stand-alone delivery system and also serve as potential development strategies for applications in a lactate environment.

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Tumor microenvironment remodeling-based penetration strategies to amplify nanodrug accessibility to tumor parenchyma

Cited by 59 publications

References 221 publications

An Updated Review on EPR-Based Solid Tumor Targeting Nanocarriers for Cancer Treatment

An Updated Review on EPR-Based Solid Tumor Targeting Nanocarriers for Cancer Treatment

Clinical Implications of Necroptosis Genes Expression for Cancer Immunity and Prognosis: A Pan-Cancer Analysis

Effection of Lactic Acid Dissociation on Swelling-Based Short-Chain Fatty Acid Vesicles Nano-Delivery

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