Liposomal Formulations to Modulate the Tumour Microenvironment and Antitumour Immune Response

Abstract

Tumours are complex systems of genetically diverse malignant cells that proliferate in the presence of a heterogeneous microenvironment consisting of host derived microvasculature, stromal, and immune cells. The components of the tumour microenvironment (TME) communicate with each other and with cancer cells, to regulate cellular processes that can inhibit, as well as enhance, tumour growth. Therapeutic strategies have been developed to modulate the TME and cancer-associated immune response. However, modulating compounds are often insoluble (aqueous solubility of less than 1 mg/mL) and have suboptimal pharmacokinetics that prevent therapeutically relevant drug concentrations from reaching the appropriate sites within the tumour. Nanomedicines and, in particular, liposomal formulations of relevant drug candidates, define clinically meaningful drug delivery systems that have the potential to ensure that the right drug candidate is delivered to the right area within tumours at the right time. Following encapsulation in liposomes, drug candidates often display extended plasma half-lives, higher plasma concentrations and may accumulate directly in the tumour tissue. Liposomes can normalise the tumour blood vessel structure and enhance the immunogenicity of tumour cell death; relatively unrecognised impacts associated with using liposomal formulations. This review describes liposomal formulations that affect components of the TME. A focus is placed on formulations which are approved for use in the clinic. The concept of tumour immunogenicity, and how liposomes may enhance radiation and chemotherapy-induced immunogenic cell death (ICD), is discussed. Liposomes are currently an indispensable tool in the treatment of cancer, and their contribution to cancer therapy may gain even further importance by incorporating modulators of the TME and the cancer-associated immune response.

The yin and yang functions of extracellular ATP and adenosine in tumor immunity

“…However, the increase of eATP and ADO comprises important components in TME, which is a complex system consisting of host derived microvasculature, stroma, endothelial cells, pericytes, fibroblasts, smooth muscle cells and immune cells, characterized further by hypoxia, acidosis and high interstitial fluid pressure [8]. The components in TME communicate with each other, and also with cancer cells, regulating cellular processes which can inhibit or promote tumor growth [9]. They participate in tumor genesis and development through various mechanisms.…”

Cationic Nanostructures for Vaccines Design

“…Their use and design for specific applications such as gene transport or as adjuvants certainly require more knowledge on their structure–function relationship. Excellent reviews are available on this nano-era regarding applications of nanotechnology in immunology [ 120 , 124 ], progress in prophylactic and therapeutic nanovaccines [ 124 ], cancer nano-immunotherapy [ 125 ], nanomaterial interactions with the immune system [ 126 ], and liposomes formulations for vaccines [ 127 , 128 ].…”

The Exploitation of Liposomes in the Inhibition of Autophagy to Defeat Drug Resistance

“…Among all different types of nanoparticles available here we will focus on liposomes, because these systems have come out as the most clinically successful, given the number of approved formulations and are widely used as drug carriers in oncological clinical setting (Belfiore et al, 2018;Gilabert-Oriol et al, 2018;Lamichhane et al, 2018;Anselmo and Mitragotri, 2019). The reasons of this success are many, such as low toxicity and immunogenicity, easy manufacturing, generally low cost, reproducibility, extreme versatility, biodegradability.…”