Nano‐Oncologicals: A Tortoise Trail Reaching New Avenues

Abstract

Research efforts towards cancer therapeutics have resulted in the development of a variety of pharmacological molecules, including small synthetic molecules and biological drugs (RNA-based therapies and monoclonal antibodies-mAbs), intended to target tumor or immune-related cells, or their signaling mediators. The majority of them present important biopharmaceutical problems related to their difficulties for overcoming biological barriers and reach their targets. Nanotechnology has been, for more than 60 years, trying to solve these problems. As knowledge in drug discovery, molecular biology, and biomaterials advances, there has been significant progress in the adequate design of nanodelivery strategies that may significantly contribute to the exploitation of the new therapies. This review provides a critical overview of the current potential of nanotechnology to solve problems associated with the different categories of drugs. Starting with the general concept of passive and active targeting, it presents the distinct advantages that delivery technologies have shown to date for improving the therapeutic outcome of small drugs with cytotoxic activity, RNA-and mAb-based therapies. Moreover, it precisely describes the benefits of combining immunotherapies and nanotechnology. The most advanced technologies are put into perspective in relation to their translational pathway and the future avenues for nano-oncologicals.

Innate and Adaptive Responses of Intratumoral Immunotherapy with Endosomal Toll-Like Receptor Agonists

“…This process leads to the recognition and elimination of cancer cells in non-injected locations (abscopal effect) [ 7 ]. Many of these experiments testing local administration of TLR ag involved their conjugation or nanoencapsulation [ 11 ].…”

“…In non-vaccine settings, systemic administration of TLR-formulations include also nanoparticles (NPs) prepared by PEGylation, conjugation with albumin, phospholipids, lipid or polymeric nanocomplexes, and encapsulation into nanocapsules, but also conjugation with antibodies or other ligands [ 11 , 57 ]. For example, intravenous administration of cyclodextrin NPs carrying resiquimod has demonstrated antitumor efficacy in MC38 colon cancer and B16.F10 melanoma mouse models [ 58 ].…”

“…These observations highlight the relevance of controlling the dose and time of administration of TLR agonists for the treatment of cancer. They also emphasize the relevance of recent nanotechnological approaches intended to improve their ability to reach the right tissular and cellular target [ 11 , 12 ].…”

Mannose-modified hyaluronic acid nanocapsules for the targeting of tumor associated macrophages

“…In parallel, nanotechnological approaches stand out for their versatility to design a large number of nanostructures adapted to different therapeutic objectives, including TAMs targeting [5,6]. In this context, lipid nanoparticles [7,8], liposomes [9][10][11][12] and polymeric nanoparticles [13,14], among other nanocarriers, have been designed to reach TAMs for prognosis purposes or as therapies to kill them, impair their protumoral functions or reprogram them towards M1-like macrophages with antitumoral activity [6,15]. Hyaluronic acid (HA) is an endogenous glycosaminoglycan, involved in the architectural structure of tissues, which has been used as a polymer to design TAM-targeted nanocarriers [16][17][18].…”

Enhancing Cancer Immunotherapeutic Efficacy with Sonotheranostic Strategies

“…Therefore, several contributions have been made in designing a functional multimodality sonosensitizer that ensure compatibility with efficient recovery against tumors. Clinical advancement of conjugating sonosensitizers in nanomedicine has resulted in significantly higher tumor inhibition and regression with sonosensitizing nanomedicines compared to the free and nonsensitized drug due to specific targeting, accumulation, and retention under US stimulation. − …”