Advanced materials for cancer treatment and beyond

Abstract

Conservative anti-cancer treatment represented by chemotherapy and surgery lacks tumor-specificity and could hardly resolve the problems associated with multidrug resistance (MDR) in cancers. Novel therapeutic materials in cancer treatment, such as those with anti-MDR or controllable treatment features, represent a significant trend due to their advantages of high and specific efficacy and timely intervention of cancer progress. In addition to their excellent biocompatibility and specificity, they can be utilized in therapies that require ease of operation, provided they are designed with high detection sensitivity. In this review, we summarize a series of recently developed materials that exhibit these advantages, including immune-enhancing and tumor microenvironment (TME)- responsive materials, and those with integrated therapeutic and imaging capabilities. We also introduce advanced modification approaches that can impart essential targeting functionalities to these materials.

Keywords: controllable treatment of cancer; integrated cancer diagnosis; materials for enhancing immunity; reversal of multidrug resistance (MDR); tumor microenvironment (TME)-responsive material.

FIGURE 1

The tree map illustrating the development of strategies for cancer treatment, with a focus on advanced materials which hold promises for reversing drug resistance, enabling controllable phototherapy, overcoming tumor microenvironment (TME) barriers, and activating immunity. They are also promising for rational design, combined therapy, and integrated diagnosis and treatment, ultimately benefiting precision cancer therapy.

FIGURE 2

Schematic illustration of PBDF NPs with enhanced anti-cancer functions. (A) Structure of PBDF NPs. PLGA-SH encapsulating BAY-1082439 or DOX were prepared as BAY-1082439@PLGA-SH or DOX@PLGA-SH NPs, respectively. These NPs were then grafted onto the Au NR cores, which were modified with FA-PEG₁₀₀₀₀-SH, resulting in the formation of PBDF NPs. (B) The rationale for PBDF NPs in inhibiting cancers with PI3K promoted MDR. The KB-C2 cancer cells overexpressing ABCB1 exhibited MDR, causing the majority of DOX to be extruded from the cells. By utilizing PBDF NPs, both DOX and BAY-1082439 are specifically delivered into tumor cells through folate receptor FR mediated targeting. This process is followed by the internalization of the nanoparticles, PLGA degradation, and drug release. Subsequently, BAY-1082439 inhibits the activity of PI3K 110 subunits, P110α and P110β, which leads to the suppression of target gene transcription and downregulation of P-gp expression. As a result, the accumulation of DOX within KB-C2 cells increases, promoting its entry into the cell nuclei, thereby interfering with DNA replication and promoting apoptosis and cell death (Lin et al., 2023). PLGA: Poly (lactic-co-glycolic acid); DOX: doxorubicin; FA: folic acid (folate); FR: folate receptor; PEG: polyethylene glycol.

FIGURE 3

BTO@NOBac for tumor piezocatalytic therapy with sustained antitumoral immunity. (A) Mechanism schematics of dendritic cell (DC) maturation and macrophage polarization, induced by the sonopiezo-catalytic therapeutic of BTO@NOBac. Under ultrasound irradiation, superoxide anions produced by the piezocatalytic reaction of BTO NPs can immediately react with nitric oxide (NO) generated from NOBac, leading to the formation of highly oxidative ONOO⁻ species in a cascade reaction. This process results in significant tumor piezocatalytic therapeutic efficacy and induces prominent and sustained antitumoral immunoactivation simultaneously. (B) Mechanism of the method for the detection of ONOO⁻ at solution level. The generation of ONOO⁻ by BTO@NOBac under ultrasound irradiation can be evaluated by using L-tyrosine. In the presence of carbon dioxide, ONOO⁻ nitrates L-tyrosine to form 3-nitrotyrosine, which emits characteristic fluorescence with an excitation wavelength of 313 nm and an emission wavelength of 406 nm (Wang L. P. et al., 2024).

FIGURE 4

Development of CT@M−E NSPC for combined PDT-chemotherapy against cancers. CT@M−E NSPC have high stability against serum disintegration and showed enhanced PDT and chemotherapeutic efficacy for cancer treatment (Chen J. et al., 2023).

FIGURE 5

Rationale design of nanomaterials for anti-cancer therapy. These materials are normally developed with targeting and environment-responsive properties. Morphological characteristics are critical for suitability in permeation and drug-release. Factors like immune system, blood vessels in tumor tissues, TME, cell skeleton and subcellular organelle, as well as biomarkers distributed in different positions of cancer cells, pH, and etc. are comprehensively assessed for target therapy on a specific patient. Real-time imaging techniques were combined for precise diagnosis.