Rademics Research Institute

Abstract

Nanoparticle-based drug delivery systems have emerged as a promising strategy in cancer immunotherapy, offering enhanced targeting, controlled release, and the ability to modulate the tumor microenvironment (TME). These nanoparticles, owing to their unique physicochemical properties, can be engineered to encapsulate therapeutic agents, such as chemotherapy drugs, immune modulators, and cytokines, and deliver them specifically to tumor cells. The manipulation of the TME, including the regulation of immune cell infiltration, hypoxic conditions, and extracellular matrix remodeling, is essential for overcoming the immune evasion mechanisms of tumors. By utilizing nanoparticles, the systemic toxicity of conventional therapies can be reduced while improving therapeutic efficacy. This chapter explores various nanoparticle platforms, including liposomes, dendrimers, micelles, and inorganic nanoparticles, highlighting their role in enhancing the immune response, promoting tumor-targeted delivery, and improving patient outcomes in cancer immunotherapy. The challenges in clinical translation, including particle design optimization, immunogenicity, and scaling, are discussed alongside the future perspectives for advancing these systems.

Introduction

The evolution of cancer treatment strategies has been significantly influenced by the rise of nanotechnology, particularly through the development of nanoparticle-based drug delivery systems [1]. These systems are engineered to encapsulate therapeutic agents and deliver them specifically to tumor cells, minimizing off-target effects and improving the therapeutic index of anticancer drugs [2]. Nanoparticles offer several advantages over traditional drug delivery systems, including enhanced stability, prolonged circulation time, and the ability to cross biological barriers [3]. The ability to control the size, shape, surface charge, and composition of nanoparticles enables tailored drug delivery that is both efficient and specific to cancer cells [4]. Moreover, the incorporation of targeting ligands and surface modifications further enhances the precision of drug delivery, allowing for targeted therapy that reduces systemic toxicity [5].

One of the most critical aspects of using nanoparticles for cancer treatment lies in their ability to modulate the tumor microenvironment (TME), which plays a pivotal role in tumor progression, immune evasion, and resistance to therapy [6]. The TME consists of various components, including stromal cells, immune cells, blood vessels, and extracellular matrix proteins [7], all of which interact to create an environment that promotes tumor growth and metastasis [8]. Nanoparticles can be engineered to target specific elements of the TME, such as immune cells, hypoxic regions, or extracellular matrix components, facilitating the modulation of the TME to support more effective immune responses and drug delivery [9]. By improving the tumor's susceptibility to treatment and enhancing the infiltration of immune cells, nanoparticles can help reverse the immunosuppressive environment that often limits the effectiveness of traditional therapies [10].

TME-modulating capabilities, nanoparticles can serve as delivery vehicles for a wide range of therapeutic agents, including chemotherapy drugs, immune checkpoint inhibitors, cytokines, and even genetic material like DNA or RNA [11]. This versatility has driven the development of various types of nanoparticles, including liposomes, dendrimers, micelles, and inorganic nanoparticles, each of which has distinct advantages in terms of drug encapsulation, stability, and biocompatibility [12]. For instance, liposomes are well-suited for encapsulating hydrophilic and hydrophobic drugs, while dendrimers offer the advantage of precise control over their size and surface functionality, enabling multi-drug loading and targeted delivery [13]. Inorganic nanoparticles, such as gold or silica-based particles, provide unique features like surface plasmon resonance [14], which can be leveraged for both therapeutic and diagnostic purposes [15].