Engineered nanoparticles for precise targeted drug delivery and enhanced therapeutic efficacy in cancer immunotherapy

Abstract

The advent of cancer immunotherapy has imparted a transformative impact on cancer treatment paradigms by harnessing the power of the immune system. However, the challenge of practical and precise targeting of malignant cells persists. To address this, engineered nanoparticles (NPs) have emerged as a promising solution for enhancing targeted drug delivery in immunotherapeutic interventions, owing to their small size, low immunogenicity, and ease of surface modification. This comprehensive review delves into contemporary research at the nexus of NP engineering and immunotherapy, encompassing an extensive spectrum of NP morphologies and strategies tailored toward optimizing tumor targeting and augmenting therapeutic effectiveness. Moreover, it underscores the mechanisms that NPs leverage to bypass the numerous obstacles encountered in immunotherapeutic regimens and probes into the combined potential of NPs when co-administered with both established and novel immunotherapeutic modalities. Finally, the review evaluates the existing limitations of NPs as drug delivery platforms in immunotherapy, which could shape the path for future advancements in this promising field.

Keywords: Blood–brain barrier; Cancer; Cancer immunotherapy; Drug delivery; Engineered nanoparticles; Nanomaterial; Nanomedicine; Tumor-barrier.

Graphical abstract

Figure 1

Designing liposomes to carry drugs for tumor immunotherapy. (A) Liposomes can carry a variety of therapeutic substances on their surface and inside. (B) Liposomes can be designed to enhance the efficacy of tumor immunotherapy in combination with PTD, SDT, and PPT. (C) Detachment of cell membranes from various cells (e.g., erythrocytes, macrophages, tumor cells) by ultrasonication, freeze-thaw, hypotonic lysis buffer, extrusion, etc. Wrapping the detached cell membrane into the liposome core surface by microfluidic electroporation, ultrasound/extrusion, and extrusion/electroporation, improving the ability of liposomes to target tumors.

Figure 2

Strategies for the treatment of tumors with diverse NPs carrying therapeutic immunological agents.

Figure 3

Strategies for the therapeutic role of NPs carrying therapeutic cargoes in the circulation. (A) The mode of transport of NPs in normal blood vessels as well as tumor vessels, in tumor vessels by enhancing the retention effect from extravasation to the tumor microenvironment, targeting tumor cell immune-related drugs will limit tumor development by destroying the tumor stroma and remodeling the tumor microenvironment. (B) NPs entering tumor cells can induce apoptosis by breaking the DNA of tumor cell nuclei, increasing the production of reactive oxygen species and autophagy, etc. Apoptotic tumor cell lysates stimulate the activation of DCs cells in the form of antigens. Activated DCs stimulate lymph nodes to produce various effector T cells (e.g., CD8T, CD4, CTL, etc.) to kill tumor cells directly, while on the other hand, these effector T cells further limit tumor development by secreting various cytokines (e.g., IL-12, IFN-γ, etc.) and GZB.

Figure 4

The structure of the blood‒brain barrier (BBB) and strategies for NPs to traverse BBB. (A) BBB consists mainly of endothelial cells tightly connected between successive cells and surrounded by a basal glycoprotein layer shared with pericytes and astrocyte ends; it maintains the central nervous system in a relatively closed state, limiting the entry of many substances to protect the central nervous system from pathogens and bacterial toxicity. (B) Diverse NPs loaded with immune-related drugs will cross the BBB through ligand-receptor-mediated, carrier-mediated, and adsorption-mediated modifications to target therapeutic drugs to tumor cells for therapeutic effects.

Figure 5

NPs combined with tumor immunotherapy strategies. (A) Diverse drug-carrying NPs. (B) Strategies for nanoparticle entry into the organism. (C) NPs that enter the body can induce immune drugs from NPs in response to specific stimuli (e.g., remote light, heat or multiple enzymes or acidic conditions in the tumor microenvironment). (D) These drugs can reverse the suppressive tumor microenvironment by increasing M1, cytotoxic T cells, or decreasing immunosuppressive cells, M2, Treg, etc., changing a “cold tumour” into a “hot tumor”.

Figure 6

NPs combined with immune cell therapy to kill tumor cells strategy. NPs induce activation of dendritic cells through antigen presentation or release of antigen to inhibit tumor development. NPs can also carry siRNA, HA, and M2PeP to promote M1 polarization of tumor-associated macrophages or inhibit M2 polarization to reshape the tumor microenvironment and inhibit tumor growth. In addition, NPs loaded with SD-208 mediate tumor killing by directly activating T cells.

Figure 7

Mechanism of NPs-mediated PDT therapy. (A) Photodynamic therapy modality diagram. (B) Under light conditions, the photosensitiser combines with oxygen TME to produce ROS, thus producing a killing effect on tumor cells. Using apoptotic tumor cells as antigens, it activates the immune response of tumor cells, thus further enhancing the killing effect on tumor cells.