Advanced drug delivery systems for oral squamous cell carcinoma: a comprehensive review of nanotechnology-based and other innovative approaches

Abstract

Oral cancer, particularly oral squamous cell carcinoma (OSCC), poses significant challenges due to its aggressiveness, high metastatic potential, and resistance to conventional therapies. Recent advancements in drug delivery systems (DDS), including nanotechnology, intelligent hydrogels, lipid nanoparticles, and photodynamic therapy (PDT), offer innovative solutions for targeted treatment. These DDS utilize tumor-specific stimuli, such as pH variations, reactive oxygen species (ROS), and enzymatic activity, to achieve precise drug release while minimizing systemic toxicity. Cutting-edge technologies, such as microelectromechanical systems (MEMS) and artificial intelligence (AI), are enhancing the precision and personalization of DDS. Combination therapies integrating chemotherapy, PDT, and immunotherapy show promise in overcoming current limitations. Despite significant progress, challenges remain in scalability, patient-specific customization, and safety assessments. This review synthesizes the state-of-the-art in DDS for OSCC, highlighting future directions and the need for interdisciplinary collaboration to improve therapeutic outcomes and patient quality of life.

Keywords: drug delivery systems; immunotherapy; intelligent hydrogels; lipid nanoparticles; nanotechnology; oral cancer; oral squamous cell carcinoma; photodynamic therapy.

Created in BioRender. Sanchez (2025) https://BioRender.com/t13g675.

FIGURE 1

In vivo synergistic antitumor effect of AuNRs@HA-g-(mPEG/Teta-co-(LA/TCPP/FA) in MCF-7 tumor-bearing nude mice. (a) Changes of relative tumor volumes of MCF-7 tumor-bearing mice after different treatments over a period of 18 days. **p < 0.01 using Student’s t-test). (b) Average weights of removed tumor sections in four treatment formulations on day 18. (c) Representative photomicrographs of H&E and TUNEL staining analysis of isolated tumor tissues after treatment in four groups. Scale bar: 100 μm (Xu et al., 2023).

FIGURE 2

(a) Schematic illustration of acid-responsive dissociation of self-assembled micelles; (b) overlaid DLS diagrams and (c) evolution of Z-average diameter of ImP micelles at 1 mg mL⁻¹, incubated at physiological pH = 7.4 and acidic pH = 5.0; and (d) %Dox release over incubation time at acidic. pHs = 5.0 and 6.8, compared with physiological pH = 7.4 (Hu and Oh, 2020).

FIGURE 3

(a) CLSM images showing the cellular distribution of DOX (red) in SCC-15 cells that were treated with NS, free DOX, NanoDOX, and NDHM at a 16 mg mL⁻¹ DOX concentration in the medium (scale bar = 25 mm); (b) the fluorescence quantitative analysis of the cellular uptake of DOX. Data represent means _ SD (n = 3), ***P < 0.001, ****P < 0.0001. (c) Relative cell viabilities of SCC-15 cells after treatments with different concentrations of DOX in HA-MMP hydrogels for 0.5 days, 1 day, 2 days, and 4 days. Data represent means _ SD (n = 3). (d) CLSM images of SCC-15 cells stained with calcein AM and Ethm-1 upon different treatments with NS, blank hydrogel, free DOX, NanoDOX, and NDHM at a 16 mg mL⁻¹ DOX concentration in the medium (scale bar = 50 mm). (e) CLSM images of SCC-15 cells stained with FITC and PI upon different treatments with NS, blank hydrogel, free DOX, NanoDOX or NDHM at a 16 mg mL⁻¹ DOX concentration in the release medium (scale bar = 50 mm) (Li et al., 2019).

FIGURE 4

AI contribution to drug development and research. AI can be used to enhance nanosystem design, expand the present drug testing modeling system, and increase the accuracy of parameter and factor selection in drug design, drug discovery, and drug repurposing methods. It also helps to better understand the mechanism of membrane interaction with the modeled human environment by studying drug permeation, simulation, human cell targets, etc., (Vora et al., 2023).

FIGURE 5

Local application of PRV111 induced robust anti-tumor response in hamster orthotopic oral cancer model. (A) Schematic representation of the experiment. (B) Golden Syrian hamsters bearing or(thotopic tumors induced by injection of HCPC-1 cell line into the cheek pouch were treated with either PBS-IP, CDDP-IP, BLK-patch or PRV111. Graphs show the average tumor volume for 6 animals per group ± SEM. P-value was performed by a 1-sided Wilcoxon Rank-sum method. Asterisk represents statistical significance between the CDDP-IP and PRV111 groups (p < 0.05). (C) Graph shows the average body weights for 6 animals per group ± SEM. Body weights of 5 tumor free animals without treatment were measure along the tumor bearing counterparts (dashed line). (D) Representative fluorescence images of tumor sections at indicated magnification taken after treatment of the hamster with PRV111 patch containing chitosan particles labeled with Cy5 (red) and encapsulating FITC (green). Yellow areas display dual-labeling, NPs with encapsulated FITC. Permeation experiment was repeated in 6 tumors (Goldberg et al., 2022).