The Role of Hitchhiking in Cancer Therapeutics—A Review

Abstract

Hitchhiking is a phenomenon of cruising on surfaces. Inspired by this process, biomimetic delivery systems leveraging the intrinsic ability of circulatory cells to target tumors exhibit considerable potential in cancer theranostics. Besides human circulatory cell‐mediated hitchhiking, bacteria‐driven hitchhiking strategies also manifest promise in cancer therapy. Such tactics are primarily built using nonpathogenic invasive bacteria with tumor homing capabilities. The chemotherapeutic cargos are hitchhiked onto the circulatory cells or bacterial spores for tumor‐targeted delivery. By integrating the benefits of such cells and therapeutic cargo, numerous efficient delivery systems that implement the notion of hitchhiking for cancer therapy are generated. Following an overview of several hitchhiking concepts, this article reviews various cellular and bacterial hitchhiking approaches for cancer treatment. Additionally, the challenges and prospects in the field of cancer theranostics related to hitchhiking are also discussed.

MRI Detection of Lymph Node Metastasis through Molecular Targeting of C–C Chemokine Receptor Type 2 and Monocyte Hitchhiking

“…MCP1 binds to CCR2 expressed by inflammatory monocytes, resulting in chemotactic migration to the metastatic LN . The inherent migration of monocytes in response to MCP1 has been reported as an effective strategy for targeted drug delivery . For example, Kuang et al developed liposomes that hitchhiked onto monocytes through CD14 binding, resulting in increased doxorubicin delivery to glioblastomas in vivo .…”

Nanomedicine Disrupts Stromal Barriers to Augment Drug Penetration for Improved Cancer Therapy†

“…[ 149‐152 ] In this process, the circulatory cells ( e.g ., T cells, neutrophils, bacteria) would act as innate “moving gears” to actively transport the coupled cargoes ( e.g ., free drugs or drug‐loaded NPs) to the deep seated tumor areas, even the poorly perfused parts of a tumor. [ 153‐158 ] In the work reported by Wang et al ., the intrinsic movement property of neutrophils was utilized to assist NPs escaping from the subendothelial void, the so‐called NPs pool. [ 159 ] They found that tumour vascular basement membrane (BM) formed a dense, cross‐linked matrix barrier surrounding the endothelium, which entrapped NPs in the perivascular pool.…”

“Nano effects”: a review on nanoparticle-induced multifarious systemic effects on cancer theranostic applications

“…Currently, lipid and polymer-based nanoparticles are used as a carrier to deliver mRNA to the tumor location 103,105,108 . These nanoformulations are safer and protect the mRNA from degradation, immunogenicity, toxicity and enhance cellular uptake undergo endosomal escape, and release the therapeutic agents into the cytosol 109 . For example, Xingfang Su et al developed lipo-polymeric nanoparticles consisting of a pH-responsive poly-(β-amino ester) (PBAE) polymeric core encapsulated with a phospholipid shell.…”

“…103,105,108 These nanoformulations are safer and protect the mRNA from degradation, immunogenicity and toxicity, and enhance cellular uptake, undergo endosomal escape, and release the therapeutic agents into the cytosol. 109 For example, Xingfang Su et al developed lipo-polymeric nanoparticles consisting of a pH-responsive poly-(b-amino ester) (PBAE) polymeric core encapsulated with a phospholipid shell. The negatively charged mRNA is held together by adsorption via ionic interactions onto the surface of positively charged nanoparticles.…”

“…103,105,108 These nanoformulations are safer and protect the mRNA from degradation, immunogenicity and toxicity, and enhance cellular uptake, undergo endosomal escape, and release the therapeutic agents into the cytosol. 109…”