Biomaterial-Based Responsive Nanomedicines for Targeting Solid Tumor Microenvironments

Abstract

Solid tumors are composed of a highly complex and heterogenic microenvironment, with increasing metabolic status. This environment plays a crucial role in the clinical therapeutic outcome of conventional treatments and innovative antitumor nanomedicines. Scientists have devoted great efforts to conquering the challenges of the tumor microenvironment (TME), in respect of effective drug accumulation and activity at the tumor site. The main focus is to overcome the obstacles of abnormal vasculature, dense stroma, extracellular matrix, hypoxia, and pH gradient acidosis. In this endeavor, nanomedicines that are targeting distinct features of TME have flourished; these aim to increase site specificity and achieve deep tumor penetration. Recently, research efforts have focused on the immune reprograming of TME in order to promote suppression of cancer stem cells and prevention of metastasis. Thereby, several nanomedicine therapeutics which have shown promise in preclinical studies have entered clinical trials or are already in clinical practice. Various novel strategies were employed in preclinical studies and clinical trials. Among them, nanomedicines based on biomaterials show great promise in improving the therapeutic efficacy, reducing side effects, and promoting synergistic activity for TME responsive targeting. In this review, we focused on the targeting mechanisms of nanomedicines in response to the microenvironment of solid tumors. We describe responsive nanomedicines which take advantage of biomaterials’ properties to exploit the features of TME or overcome the obstacles posed by TME. The development of such systems has significantly advanced the application of biomaterials in combinational therapies and in immunotherapies for improved anticancer effectiveness.

Cetuximab chemotherapy resistance: Insight into the homeostatic evolution of head and neck cancer (Review)

“…Although immunotherapy has proved to be a valuable approach to treat different cancer types, including HNSCC, it induces drug resistance ( 148 ) and is limited to tumors showing appropriated levels of immunogenicity. Nanomedicines promise to circumvent this limitation, improving, for example, the release and presentation of tumor antigens in cases with low immunogenicity ( 149 , 150 ). Tissue editing approaches, which reprogram cancer hallmarks into biologic hallmarks, may also bring new tools to circumvent tumor heterogeneity and therapy resistance by using continuous low-dose chemotherapy for inducing stress responses, and transcriptional modulators for inflammation control ( 151 ).…”

Nanostructured Biomaterials in Tumor Tissue Engineering: Regenerative Medicine and Immunotherapies

“…These features lead cancer cells to a phenotype selection associated with genetic rearrangement, M2 anti-inflammatory polarization, and genomic instability that affects the ECM, blood vessels and tumor stroma development. Thus, increased research interest has been devoted to the development of responsive nanostructured medicines for TME [14].…”

“…The high heterogeneity and abnormal vasculature of TME promote disturbed blood flow accompanied with distorted hydrostatic and osmotic pressure in the blood vessels, further promoting neovascularization and tumor hypoxia. The dynamic nature of TME has a profound effect on impaired cellular signaling promoting the generation of multiple gene mutations, the M2 anti-inflammatory phenotype of macrophages and immunosuppression [14]. The nature of TME imposed important obstacles in the effective delivery of therapeutics at the tumor site promoting inadequate tumor treatment.…”