Combinations of chemo-, immuno-, and gene therapies using nanocarriers as a multifunctional drug platform

ABSTRACT

Introduction

Cancer immunotherapies have created a new generation of therapeutics to employ the immune system to attack cancer cells. However, these therapies are typically based on biologics that are nonspecific and often exhibit poor tumor penetration and dose-limiting toxicities. Nanocarriers allow the opportunity to overcome these barriers as they have the capabilities to direct immunomodulating drugs to tumor sites via passive and active targeting, decreasing potential adverse effects from nonspecific targeting. In addition, nanocarriers can be multifunctionalized to deliver multiple cancer therapeutics in a single drug platform, offering synergistic potential from co-delivery approaches.

Areas covered

This review focuses on the delivery of cancer therapeutics using emerging nanocarriers to achieve synergistic results via co-delivery of immune-modulating components (i.e. chemotherapeutics, monoclonal antibodies, and genes).

Expert opinion

Nanocarrier-mediated delivery of combinatorial immunotherapy creates the opportunity to fine-tune drug release while achieving superior tumor targeting and tumor cell death, compared to free drug counterparts. As these nanoplatforms are constantly improved upon, combinatorial immunotherapy will afford the greatest benefit to treat an array of tumor types while inhibiting cancer evasion pathways.

KEYWORDS:

• Cancer
• chemoimmunotherapy
• delivery
• gene
• immunotherapy
• nanomedicine
• nanoparticle
• nanocarrier

Article highlights

• Cancer immunotherapies are being used to combat the limitations of conventional cancer treatments, including small-molecule therapeutics, by modulating the immune system to fight cancer.

• The combination of immunotherapeutics, specifically those targeting HER2 and PD-1/PD-L1, with nanocarriers encapsulating chemotherapeutics has synergistic effects and demonstrates enhanced efficacy.

• Immunotherapeutic ligands can be co-delivered with genes to provide synergy in tumor inhibition by attacking multiple hallmarks of cancer.

• Nanocarriers can be multifunctionalized to deliver genes and small molecule drugs ligands to inhibit multidrug resistance or dually attack pro-tumorigenic pathways

• The development of personalized medicine enabled by multifunctional nanocarriers will allow for the creation of cancer therapy cocktails that elicit the highest impact for a wide range of patients.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This study was partially supported by National Science Foundation (NSF) under grant # DMR-1808251 and 2211932. The authors also acknowledge the partial support from NCI/NIH under grant # 1R01CA260140, the Wisconsin Head & Neck Cancer SPORE Grant from NIH [P50-DE026787], The Falk Medical Research Trust – Catalyst and Transformational Awards Program, and Milton J. Henrichs Chair Funds provided to S Hong. In addition, Q Hu acknowledges the start-up package support from University of Wisconsin-Madison.