Evidence map›Paper›PMID 42387117›Full record

ArticlePharmaceutical research2026

Leveraging Carnitine-functionalized Lipid Nanocarrier based Targeted Delivery of A1874 PROTAC for Glioblastoma.

Himaxi Patel, Xiang Chen, Afsin Malik, Kareena S Poonai, Zhe-Sheng Chen, Sei Higuchi, Ketan Patel

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Article in Pharmaceutical research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

7 authors.

Himaxi PatelCollege of Pharmacy and Health Sciences, St. John's University, St. Albert Hall, B-49, 8000 Utopia Parkway, Queens, NY, 11432, USA.
Xiang ChenCollege of Pharmacy and Health Sciences, St. John's University, St. Albert Hall, B-49, 8000 Utopia Parkway, Queens, NY, 11432, USA.
Afsin MalikCollege of Pharmacy and Health Sciences, St. John's University, St. Albert Hall, B-49, 8000 Utopia Parkway, Queens, NY, 11432, USA.
Kareena S PoonaiCollege of Pharmacy and Health Sciences, St. John's University, St. Albert Hall, B-49, 8000 Utopia Parkway, Queens, NY, 11432, USA.
Zhe-Sheng ChenCollege of Pharmacy and Health Sciences, St. John's University, St. Albert Hall, B-49, 8000 Utopia Parkway, Queens, NY, 11432, USA.
Sei HiguchiCollege of Pharmacy and Health Sciences, St. John's University, St. Albert Hall, B-49, 8000 Utopia Parkway, Queens, NY, 11432, USA.
Ketan PatelCollege of Pharmacy and Health Sciences, St. John's University, St. Albert Hall, B-49, 8000 Utopia Parkway, Queens, NY, 11432, USA. patelk2@stjohns.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeGlioblastoma(GBM) is highly aggressive and therapeutically refractory brain malignancy. Despite maximal intervention, patient prognosis remains dismal. A major obstacle in its management is the limited permeation of therapeutic agents across the blood-brain barrier(BBB), further intensified by resistance to standard chemotherapy such as temozolomide(TMZ). Proteolysis-targeting chimeras(PROTACs), offer new opportunities by enabling selective degradation of oncogenic proteins. A1874, a heterobifunctional molecule, has demonstrated potent, selective degradation of oncogenic driver-BRD4 in pancreatic, breast, and colon cancer. BRD4 drives GBM cell proliferation, survival, and resistance to therapy; therefore, we investigated the therapeutic potential of A1874 in brain cancer.

methodsHerein, we developed brain-targeted self-nanoemulsifying drug delivery system, termed PRONano, designed to enhance the targeted delivery of A1874. The system is functionalized with Palmitoyl-DL-carnitine chloride(PC) to facilitate transport across the BBB. Physicochemical characterization was performed to assess particle size. In-vitro cytotoxicity, qualitative and quantitative cellular uptake was analyzed. Mechanistic validation was conducted using western blot and qPCR, while 3D spheroid assay was employed to assess efficacy in tumor-mimicking microenvironment.

resultsPRONano exhibited nanoscale particle size and significantly enhanced intracellular uptake of A1874. Formulation exhibited enhanced cytotoxicity in temozolomide-sensitive and resistant GBM cells. Effective BRD4 protein degradation was identified in the Western blot. PRONano significantly inhibited 3-D spheroid tumor growth suggesting better penetration and efficacy in tumor-like microenvironment.

conclusionsPRONano is brain-targeted, rationally designed nanoformulation which can overcome major A1874 delivery constraints. This strategy augmented PROTAC delivery and therapeutic potential in GBM, supporting future preclinical development.

Indexed as

Antineoplastic AgentsBrain NeoplasmsGlioblastomaNanoparticlesBlood-Brain BarrierBromodomain Containing ProteinsCell Cycle ProteinsCell Line, TumorDrug CarriersDrug Delivery SystemsHumansLipidsNanoparticle Drug Delivery SystemParticle SizeProteolysis Targeting ChimeraTemozolomideAntineoplastic AgentsBRD4 protein, humanBromodomain Containing ProteinsCell Cycle ProteinsDrug CarriersLipidsNanoparticle Drug Delivery SystemProteolysis Targeting ChimeraTemozolomideTranscription Factorsblood–brain barrierBRD4 degradationglioblastomaPROTACstargeted nanoformulation

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.