Monotherapy and Combination Therapy Using Anti‐Angiogenic Nanoagents to Fight Cancer

Liang, Pingping; Ballou, Byron; Lv, Xinyi; Si, Weili; Bruchez, Marcel P.; Huang, Wei; Dong, Xiaochen

doi:10.1002/adma.202005155

Cited by 92 publications

(53 citation statements)

References 222 publications

(227 reference statements)

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“…The choice can be monotherapy or combination therapy and depends on several factors like cancer origin, stage, location, and grade. 1 Even though these anticancer therapies can be effective, they have certain disadvantages, like: (a) they can cause pharmacological adverse effects at normal tissues; (b) they lack the ability of center-point targeting deep within tumor mass; (c) they mostly acquire drug resistance and are unable to eradicate the entire cancer cell population in the tumor. 2 Hence, there is an utmost need to develop some innovative therapeutics that should be simple, cost-effective, and could serve as a substitute to conventional treatments to fight cancer.…”

Section: Introductionmentioning

confidence: 99%

Innovative Approaches of Engineering Tumor-Targeting Bacteria with Different Therapeutic Payloads to Fight Cancer: A Smart Strategy of Disease Management

Allemailem¹

2021

IJN

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Conventional therapies for cancer eradication like surgery, radiotherapy, and chemotherapy, even though most widely used, still suffer from some disappointing outcomes. The limitations of these therapies during cancer recurrence and metastasis demonstrate the need for better alternatives. Some bacteria preferentially colonize and proliferate inside tumor mass; thus these bacteria can be used as ideal candidates to deliver antitumor therapeutic agents. The bacteria like Bacillus spp., Clostridium spp., E. coli, Listeria spp., and Salmonella spp. can be reprogrammed to produce, transport, and deliver anticancer agents, eg, cytotoxic agents, prodrug converting enzymes, immunomodulators, tumor stroma targeting agents, siRNA, and drug-loaded nanoformulations based on clinical requirements. In addition, these bacteria can be genetically modified to express various functional proteins and targeting ligands that can enhance the targeting approach and controlled drug-delivery. Low tumor-targeting and weak penetration power deep inside the tumor mass limits the use of anticancer drug-nanoformulations. By using anticancer drug nanoformulations and other therapeutic payloads in combination with antitumor bacteria, it makes a synergistic effect against cancer by overcoming the individual limitations. The tumor-targeting bacteria can be either used as a monotherapy or in addition with other anticancer therapies like photothermal therapy, photodynamic therapy, and magnetic field therapy to accomplish better clinical outcomes. The toxicity issues on normal tissues is the main concern regarding the use of engineered antitumor bacteria, which requires deeper research. In this article, the mechanism by which bacteria sense tumor microenvironment, role of some anticancer agents, and the recent advancement of engineering bacteria with different therapeutic payloads to combat cancers has been reviewed. In addition, future prospective and some clinical trials are also discussed.

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Section: Introductionmentioning

confidence: 99%

Innovative Approaches of Engineering Tumor-Targeting Bacteria with Different Therapeutic Payloads to Fight Cancer: A Smart Strategy of Disease Management

Allemailem¹

2021

IJN

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“…Accumulating evidence have reported that antiangiogenic agents decrease the immunosuppression by modulating tumor microenvironment (TME) and exhibit synergetic effects when combined with immunotherapies [14]. Previous studies have shown that apatinib exerts its immunomodulatory activity in several tumor types.…”

Section: Introductionmentioning

confidence: 99%

Apatinib triggers autophagic and apoptotic cell death via VEGFR2/STAT3/PD-L1 and ROS/Nrf2/p62 signaling in lung cancer

Xie

Zhou

Liang

et al. 2021

J Exp Clin Cancer Res

114

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Background Recently, a variety of clinical trials have shown that apatinib, a small-molecule anti-angiogenic drug, exerts promising inhibitory effects on multiple solid tumors, including non-small cell lung cancer (NSCLC). However, the underlying molecular mechanism of apatinib on NSCLC remains unclear. Methods MTT, EdU, AO/EB staining, TUNEL staining, flow cytometry, colony formation assays were performed to investigate the effects of apatinib on cell proliferation, cell cycle distribution, apoptosis and cancer stem like properties. Wound healing and transwell assays were conducted to explore the role of apatinib on migration and invasion. The regulation of apatinib on VEGFR2/STAT3/PD-L1 and ROS/Nrf2/p62 signaling were detected. Furthermore, we collected conditioned medium (CM) from A549 and H1299 cells to stimulate phorbol myristate acetate (PMA)-activated THP-1 cells, and examined the effect of apatinib on PD-L1 expression in macrophages. The Jurkat T cells and NSCLC cells co-culture model was used to assess the effect of apatinib on T cells activation. Subcutaneous tumor formation models were established to evaluate the effects of apatinib in vivo. Histochemical, immunohistochemical staining and ELISA assay were used to examine the levels of signaling molecules in tumors. Results We showed that apatinib inhibited cell proliferation and promoted apoptosis in NSCLC cells in vitro. Apatinib induced cell cycle arrest at G1 phase and suppressed the expression of Cyclin D1 and CDK4. Moreover, apatinib upregulated Cleaved Caspase 3, Cleaved Caspase 9 and Bax, and downregulated Bcl-2 in NSCLC cells. The colony formation ability and the number of CD133 positive cells were significantly decreased by apatinib, suggesting that apatinib inhibited the malignant and stem-like features of NSCLC cells. Mechanistically, apatinib inhibited PD-L1 and c-Myc expression by targeting VEGFR2/STAT3 signaling. Apatinib also inhibited PD-L1 expression in THP-1 derived macrophages stimulated by CM from NSCLC cells. Furthermore, apatinib pretreatment increased CD69 expression and IFN-γ secretion in stimulated Jurkat T cells co-cultured with NSCLC cells. Apatinib also promoted ROS production and inhibited Nrf2 and p62 expression, leading to the autophagic and apoptotic cell death in NSCLC. Moreover, apatinib significantly inhibited tumor growth in vivo. Conclusion Our data indicated that apatinib induced autophagy and apoptosis in NSCLC via regulating VEGFR2/STAT3/PD-L1 and ROS/Nrf2/p62 signaling.

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“…Anti-angiogenic drugs have also been shown to improve drug delivery efficacy and deeper drug penetration [34][35][36]. In recent reviews [37][38][39], normalization induced by anti-angiogenesis in combination with chemotherapy was introduced as a promising strategy in cancer treatment. Few numerical studies have been performed on drug delivery under the influence of antiangiogenesis-induced vascular normalization.…”

Section: Introductionmentioning

confidence: 99%

Numerical Investigation on the Anti-Angiogenic Therapy-Induced Normalization in Solid Tumors

et al. 2022

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This study numerically analyzes the fluid flow and solute transport in a solid tumor to comprehensively examine the consequence of normalization induced by anti-angiogenic therapy on drug delivery. The current study leads to a more accurate model in comparison to previous research, as it incorporates a non-homogeneous real-human solid tumor including necrotic, semi-necrotic, and well-vascularized regions. Additionally, the model considers the effects of concurrently chemotherapeutic agents (three macromolecules of IgG, F(ab′)2, and F(ab′)) and different normalization intensities in various tumor sizes. Examining the long-term influence of normalization on the quality of drug uptake by necrotic area is another contribution of the present study. Results show that normalization decreases the interstitial fluid pressure (IFP) and spreads the pressure gradient and non-zero interstitial fluid velocity (IFV) into inner areas. Subsequently, wash-out of the drug from the tumor periphery is decreased. It is also demonstrated that normalization can improve the distribution of solute concentration in the interstitium. The efficiency of normalization is introduced as a function of the time course of perfusion, which depends on the tumor size, drug type, as well as normalization intensity, and consequently on the dominant mechanism of drug delivery. It is suggested to accompany anti-angiogenic therapy by F(ab′) in large tumor size (Req=2.79 cm) to improve reservoir behavior benefit from normalization. However, IgG is proposed as the better option in the small tumor (Req=0.46 cm), in which normalization finds the opportunity of enhancing uniformity of IgG average exposure by 22%. This study could provide a perspective for preclinical and clinical trials on how to take advantage of normalization, as an adjuvant treatment, in improving drug delivery into a non-homogeneous solid tumor.

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Monotherapy and Combination Therapy Using Anti‐Angiogenic Nanoagents to Fight Cancer

Cited by 92 publications

References 222 publications

Innovative Approaches of Engineering Tumor-Targeting Bacteria with Different Therapeutic Payloads to Fight Cancer: A Smart Strategy of Disease Management

Innovative Approaches of Engineering Tumor-Targeting Bacteria with Different Therapeutic Payloads to Fight Cancer: A Smart Strategy of Disease Management

Apatinib triggers autophagic and apoptotic cell death via VEGFR2/STAT3/PD-L1 and ROS/Nrf2/p62 signaling in lung cancer

Numerical Investigation on the Anti-Angiogenic Therapy-Induced Normalization in Solid Tumors

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