Journal Article

AI-guided design of a CXCR4-targeted core-shell nanocarrier for co-delivery of berberine/paclitaxel in cancer therapy

Park, Hansoo, Jang, Yeonwoo, Park, In-Kyu, Vasukutty, Arathy, J. Moon, James, Babu, Amal, Chahal, Sahil

2025

Overview

An integrated three-step artificial-intelligence (AI) workflow was developed to accelerate the design of a CXCR4-targeted, dual-drug nanocarrier for colorectal cancer therapy. The workflow combined AI-based drug synergy prediction, peptide ligand discovery, and formulation optimization to create a core-shell nanocarrier consisting of a mesoporous silica core coated with a liposomal shell, co-delivering berberine (BBR) and paclitaxel (PTX). The nanocarrier exhibited efficient drug loading, sustained release, and selective uptake by CXCR4-positive cancer cells. In vitro, it synergistically inhibited cancer proliferation and migration, while in vivo it produced pronounced tumor regression and reversal of tumor-associated splenomegaly without systemic toxicity. These findings demonstrate that AI-guided synergy scouting and modular nanocarrier engineering can yield a receptor-targeted combination therapy with translational potential for next-generation cancer treatment.  Graphical abstract AI-guided, CXCR4-targeted liposome-mesoporous silica nanocarriers co-load berberine and paclitaxel, sustaining dual release and markedly suppressing tumor growth without systemic toxicity.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: AI-guided nanomedicine / Animals / Apoptosis / Artificial intelligence / Berberine / Berberine - chemistry / Berberine - pharmacology / Biocompatibility / Biotechnology / Cancer / Cancer therapies / Cell Line, Tumor / Cell proliferation / Cell Proliferation - drug effects / Chemistry / Chemistry and Materials Science / Chemotherapy / Colorectal cancer / Colorectal carcinoma / Combination chemotherapy / Controlled release / CXCR4 protein / CXCR4-targeted core-shell / Cytotoxicity / Drug Carriers - chemistry / Drug Delivery Systems / Drug development / Drug Liberation / Drug therapy, Combination / Health aspects / Humans / Hydration / Kinases / Ligands / Lipids / Liposome coating / Liposomes - chemistry / Medical prognosis / Mesoporous silica nanoparticle / Mice / Mice, Inbred BALB C / Mice, Nude / Modular engineering / Molecular Medicine / Nanoparticles / Nanoparticles - chemistry / Nanotechnology / Paclitaxel / Paclitaxel - chemistry / Paclitaxel - pharmacology / Patient outcomes / Peptides / Permeability / Proteins / Receptors, CXCR4 - metabolism / Silicon dioxide / Silicon Dioxide - chemistry / Splenomegaly / Sustained release / Therapy / Toxicity / Tumors / Workflow