Modulating the tumor microenvironment with new therapeutic nanoparticles: A promising paradigm for tumor treatment

Zhang, Yinlong; Ho, Shih‐Hsin; Li, Bozhao; Nie, Guangjun; Li, Suping

doi:10.1002/med.21644

Cited by 32 publications

(27 citation statements)

References 95 publications

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“…The tumor microenvironment is related to tumor progression and affects tumor growth, metastasis, drug resistance and recurrence ( 53 ). The regulation of the microenvironment for tumors has also become a new strategy for cancer treatment ( 54 ).…”

Section: Discussionmentioning

confidence: 99%

Propofol induces apoptosis and ameliorates 5‑fluorouracil resistance in OSCC cells by reducing the expression and secretion of amphiregulin

et al. 2021

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among the different types of oral cancer, >90% of cases are oral squamous cell carcinoma (OSCC). 5-fluorouracil (5-Fu) is a commonly used treatment for oScc, but cells typically display resistance to the drug. Propofol, an intravenous anesthetic agent, exhibits certain anticancer effects, including the inhibition of cancer cell proliferation, migration and invasion. Secreted proteins, such as growth factors and cytokines are involved in cancer development and progression, but the effect of propofol on secreted proteins in oScc is not completely understood. an MTT assay, flow cytometry and western blotting were performed to determine the anticancer effects of propofol. The secretion profile of OSCC was determined using an antibody array, and clinical importance was assessed using the Gene expression Profiling Interactive Analysis database. The results were verified by performing reverse transcription-quantitative Pcr (rT-qPcr) and western blotting. 5-Fu-resistant cells were established to determine the role of the gene of interest in drug resistance. The results demonstrated that propofol decreased cell viability and promoted cell apoptosis. The antibody array results showed that propofol attenuated the secretion of multiple growth factors. The bioinformatics results indicated that amphiregulin (areG) was expressed at significantly higher levels in cancer tissues, which was also related to poor prognosis. The results of rT-qPcr and western blotting revealed that propofol decreased areG expression. Pretreatment with exogenous recombinant areG increased eGFr activation and conferred propofol resistance. Moreover, the results indicated that the expression and activation of areG was also related to 5-Fu resistance, but propofol ameliorated 5-Fu drug resistance. Therefore, the present study suggested that propofol combination therapy may serve as an effective treatment strategy for oScc.

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Section: Discussionmentioning

confidence: 99%

Propofol induces apoptosis and ameliorates 5‑fluorouracil resistance in OSCC cells by reducing the expression and secretion of amphiregulin

et al. 2021

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“…One option investigators have researched for dealing with the troubles caused by the stroma is to target inhibiting factors, such as fibroblasts, within the stroma by using NPs [109][110][111]. This method focuses on decreasing the mass associated with fibroblasts so that there would be greater perfusion for drug delivery [110][111][112][113]. One such study used a docetaxel NP conjugate composed of PEGylated and acetylated carboxymethylcellulose to target fibroblasts in an orthotopic murine breast cancer model [114].…”

Section: Stromamentioning

confidence: 99%

Complex Factors and Challenges that Affect the Pharmacology, Safety and Efficacy of Nanocarrier Drug Delivery Systems

et al. 2021

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Major developments in nanomedicines, such as nanoparticles (NPs), nanosomes, and conjugates, have revolutionized drug delivery capabilities over the past four decades. Although nanocarrier agents provide numerous advantages (e.g., greater solubility and duration of systemic exposure) compared to their small-molecule counterparts, there is considerable inter-patient variability seen in the systemic disposition, tumor delivery and overall pharmacological effects (i.e., anti-tumor efficacy and unwanted toxicity) of NP agents. This review aims to provide a summary of fundamental factors that affect the disposition of NPs in the treatment of cancer and why they should be evaluated during preclinical and clinical development. Furthermore, this chapter will highlight some of the translational challenges associated with elements of NPs and how these issues can only be addressed by detailed and novel pharmacology studies.

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“…[ 1 ] In this regard, targeting inhibitory receptors on cytotoxic T cells and/or tumor cells can constructively reinvigorate antitumor immune responses in the tumor microenvironment (TME) and partially modulate the immunosuppressive microenvironment of tumors. [ 2,3 ] Programmed cell death ligand‐1 (PD‐L1) is known as one of these inhibitory receptors on cancerous cells which engages in the PD‐1/PD‐L1 axis and subsequently prevents the killing capacity of T cells. [ 4 ] Interference with the PD‐1/PD‐L1 interaction using immune checkpoint inhibitors (ICIs) such as monoclonal antibodies or specific peptide sequences have an effective impact on the enhancement of antitumor immune responses.…”

Section: Introductionmentioning

confidence: 99%

Bifunctional Therapeutic Peptide Assembled Nanoparticles Exerting Improved Activities of Tumor Vessel Normalization and Immune Checkpoint Inhibition

Taleb

Atabakhshi‐Kashi

Wang

et al. 2021

Adv Healthcare Materials

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The effectiveness of cancer immunotherapy is impaired by the dysfunctional vasculature of tumors. Created hypoxia zones and limited delivery of cytotoxic immune cells help to have immune resistance in tumor tissue. Structural and functional normalization of abnormal tumor vasculature provide vessels for more perfusion efficiency and drug delivery that result in alleviating the hypoxia in the tumor site and increasing infiltration of antitumor T cells. Taking advantage of peptide amphiphiles, herein, a novel peptide amphiphile nanoparticle composed of an antiangiogenic peptide (FSEC) and an immune checkpoint blocking peptide (DPPA) is designed and characterized. FSEC peptide is known to be involved in vessel normalization of tumors in vivo. DPPA is an inhibitory peptide of the PD‐1/PD‐L1 immune checkpoint pathway. The peptide amphiphile nanoparticle sets out to test whether simultaneous modulation of tumor vasculature and immune systems in the tumor microenvironment has a synergistic effect on tumor suppression. Increased intratumoral infiltration of immune cells following vascular normalization, and simultaneously blocking the immune checkpoint function of PD‐L1 reactivates effective immune responses to the tumors. In summary, the current study provides a new perspective on the regulation of tumor vessel normalization and immunotherapy based on functional peptide nanoparticles as nanomedicine for improved therapeutic purposes.

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Modulating the tumor microenvironment with new therapeutic nanoparticles: A promising paradigm for tumor treatment

Cited by 32 publications

References 95 publications

Propofol induces apoptosis and ameliorates 5‑fluorouracil resistance in OSCC cells by reducing the expression and secretion of amphiregulin

Propofol induces apoptosis and ameliorates 5‑fluorouracil resistance in OSCC cells by reducing the expression and secretion of amphiregulin

Complex Factors and Challenges that Affect the Pharmacology, Safety and Efficacy of Nanocarrier Drug Delivery Systems

Bifunctional Therapeutic Peptide Assembled Nanoparticles Exerting Improved Activities of Tumor Vessel Normalization and Immune Checkpoint Inhibition

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