A nanoengineered topical transmucosal cisplatin delivery system induces anti-tumor response in animal models and patients with oral cancer.
A nanoengineered topical transmucosal cisplatin delivery system induces anti-tumor response in animal models and patients with oral cancer.
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DOI：
10.1038/s41467-022-31859-3
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发表时间：
2022-08-17
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
Despite therapeutic advancements, oral cavity squamous cell carcinoma (OCSCC) remains a difficult disease to treat. Systemic platinum-based chemotherapy often leads to dose-limiting toxicity (DLT), affecting quality of life. PRV111 is a nanotechnology-based system for local delivery of cisplatin loaded chitosan particles, that penetrate tumor tissue and lymphatic channels while avoiding systemic circulation and toxicity. Here we evaluate PRV111 using animal models of oral cancer, followed by a clinical trial in patients with OCSCC. In vivo, PRV111 results in elevated cisplatin retention in tumors and negligible systemic levels, compared to the intravenous, intraperitoneal or intratumoral delivery. Furthermore, PRV111 produces robust anti-tumor responses in subcutaneous and orthotopic cancer models and results in complete regression of carcinogen-induced premalignant lesions. In a phase 1/2, open-label, single-arm trial (NCT03502148), primary endpoints of efficacy (≥30% tumor volume reduction) and safety (incidence of DLTs) of neoadjuvant PRV111 were reached, with 69% tumor reduction in ~7 days and over 87% response rate. Secondary endpoints (cisplatin biodistribution, loco-regional control, and technical success) were achieved. No DLTs or drug-related serious adverse events were reported. No locoregional recurrences were evident in 6 months. Integration of PRV111 with current standard of care may improve health outcomes and survival of patients with OCSCC. Cisplatin is the most frequently used chemotherapeutic agent for the treatment of patients with oral cavity squamous cell carcinoma (OCSCC), however, systemic administration is often associated with dose limiting side effects. Here the authors design and test a nano-engineered patch system (PRV111) for the local delivery of cisplatin-loaded chitosan nanoparticles and report the results of a phase 1/2 clinical trial of PRV111 in patients with OCSCC.
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影响因子：
8.8
作者：
Balermpas, P;Michel, Y;Wagenblast, J;Seitz, O;Weiss, C;Rodel, F;Rodel, C;Fokas, E
通讯作者：
Fokas, E
影响因子：
158.5
作者：
Brizel, DM;Albers, ME;Prosnitz, LR
通讯作者：
Prosnitz, LR
影响因子：
3.2
作者：
Chow, Shein-Chung;Tu, Yi-Hsuan
通讯作者：
Tu, Yi-Hsuan
DOI：
10.1002/hed.24935
发表时间：
2018-01-01
影响因子：
2.9
作者：
Davidi, Erez Shmuel;Dreifuss, Tamar;Popovtzer, Rachela
通讯作者：
Popovtzer, Rachela
影响因子：
4.7
作者：
Broner EC;Trujillo JA;Korzinkin M;Subbannayya T;Agrawal N;Ozerov IV;Zhavoronkov A;Rooper L;Kotlov N;Shen L;Pearson AT;Rosenberg AJ;Savage PA;Mishra V;Chatterjee A;Sidransky D;Izumchenko E
通讯作者：
Izumchenko E