Recent Advances in Nanoscale Sprayable Hydrogels for Cancer Management: Nanoparticle-Loaded Formulations for Therapy and Prevention

Jae Min Lee,1,* Su Jeong Kang,1,* Moon Sup Yoon,1 Min Jeong Jo,2 Myeong Kyun Yoo,1 So Yeon Park,1 Sunghyun Bong,1 Jonghyuk Kim,1 Seonmin Park,1 Yeseung Lee,1 Yuseon Shin,1 Hye Jin Lee,1 Jin-Seok Kim,3 Chun-Woong Park,1 Dae Hwan Shin1,4 1College of Pharmacy, Chungbuk National University, Cheongju, Chungcheongbuk-do, 28160, Republic of Korea; 2Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS, 66047, USA; 3Drug Information Research Institute (DIRI), College of Pharmacy, Sookmyung Women’s University, Seoul, 04310, Republic of Korea; 4Chungbuk National University Hospital, Chungbuk National University, Cheongju, Chungcheongbuk-do, 28644, Republic of Korea*These authors contributed equally to this workCorrespondence: Chun-Woong Park; Dae Hwan Shin, College of Pharmacy, Chungbuk National University, Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju, Chungcheongbuk-do, 28160, Republic of Korea, Tel +82 43 261 3330 ; +82 43 261 2820, Fax +82 43 268 2732, Email cwpark@chungbuk.ac.kr; dshin@chungbuk.ac.krAbstract: Sprayable hydrogels represent an emerging class of nanoscale, localized drug delivery systems in oncology, offering rapid in situ gelation, strong tissue adhesion, and minimally invasive administration. Recent advances have integrated nanotechnology into sprayable hydrogel formulations to enhance therapeutic efficacy at tumor sites through various strategies, including nanoemulsions, nanocomposites, nanoparticle-loaded matrices, nanovaccines, and nanosprays. Across preclinical models, these platforms have demonstrated quantitative improvements, including up to 70– 95% reductions in residual tumor burden, 2– 5-fold increases in intratumoral drug retention, and survival extensions ranging from 30% to over 60% compared with free-drug controls. These platforms have demonstrated the ability to eliminate residual tumor cells, activate antitumor immunity, and prevent recurrence at surgical margins or mucosal interfaces. Therapeutic modalities include the controlled release of chemotherapeutics, immune checkpoint inhibitors, and metabolic or oxidative regulators, all delivered within nanostructured hydrogel matrices. Several systems also reported over 80% suppression of local recurrence at surgical margins and significant potentiation of immune activation markers such as CD8⁺ T-cell infiltration and dendritic cell maturation. Nanoscale sprayable hydrogels have shown promise across diverse clinical applications, including peritoneal carcinomatosis, superficial skin tumors, and premalignant mucosal lesions. The hydrogels themselves comprise a wide range of nanostructured materials, such as thermosensitive polymers, self-gelling powders, supramolecular assemblies, and nanoparticle-laden scaffolds, that enable precise spatial and temporal control of drug delivery. In this review, we categorize these systems based on cancer type, underlying mechanisms of action, and therapeutic goals (treatment vs prevention). By integrating nanotechnology, immunotherapy, and tissue-responsive design, nanoscale sprayable hydrogels represent a modular and adaptable platform for personalized cancer care, with compatibility across surgical, endoscopic, and topical administration routes. However, despite these advances, the clinical translation of sprayable hydrogels remains limited by challenges such as sterilization constraints, device–material compatibility issues, storage and handling stability, and regulatory hurdles, all of which must be systematically addressed to enable widespread clinical adoption. Keywords: sprayable hydrogel, localized drug delivery, postoperative cancer therapy, cancer immunotherapy, precancerous lesion prevention