biostudies-literatureMu QNIBIB NIH HHSOffice of Extramural Research, National Institutes of HealthNCI NIH HHSNIH HHS10-23https://www.ebi.ac.uk/biostudies/studies/S-EPMC7944405biostudies-literatureUnknown38Systemic delivery of hydrophobic anti-cancer drugs with nanocarriers, particularly for drug-resistant and metastatic cancer, remain a challenge because of the difficulty to achieve high drug loading, while maintaining a small hydrodynamic size and colloid stability in blood to ensure delivery of an efficacious amount of drug to tumor cells. Here we introduce a new approach to address this challenge. In this approach, nanofibers of larger size with good drug loading capacity are first constructed by a self-assembly process, and upon intravascular injection and interacting with serum proteins in vivo, these nanofibers break down into ultra-fine nanoparticles of smaller size that inherit the drug loading property from their parent nanofibers. We demonstrate the efficacy of this approach with a clinically available anti-cancer drug: paclitaxel (PTX). In vitro, the PTX-loaded nanoparticles enter cancer cells and induce cellular apoptosis. In vivo, they demonstrate prolonged circulation in blood, induce no systemic toxicity, and show high potency in inhibiting tumor growth and metastasis in both mouse models of aggressive, drug-resistant breast cancer and melanoma. This study points to a new strategy toward improved anti-cancer drug delivery and therapy.Materials today (Kidlington, England)In vivo Serum Enabled Production of Ultrafine Nanotherapeutics for Cancer Treatment.PMC7944405R01 CA161953T32 CA138312S10 OD016240R01 EB026890S10 OD010652Chung SGebhart RNLin GZhang MWang HMu QPatton VKStephen ZRfalseIn vivo Serum Enabled Production of Ultrafine Nanotherapeutics for Cancer Treatment.Systemic delivery of hydrophobic anti-cancer drugs with nanocarriers, particularly for drug-resistant and metastatic cancer, remain a challenge because of the difficulty to achieve high drug loading, while maintaining a small hydrodynamic size and colloid stability in blood to ensure delivery of an efficacious amount of drug to tumor cells. Here we introduce a new approach to address this challenge. In this approach, nanofibers of larger size with good drug loading capacity are first constructed by a self-assembly process, and upon intravascular injection and interacting with serum proteins in vivo, these nanofibers break down into ultra-fine nanoparticles of smaller size that inherit the drug loading property from their parent nanofibers. We demonstrate the efficacy of this approach with a clinically available anti-cancer drug: paclitaxel (PTX). In vitro, the PTX-loaded nanoparticles enter cancer cells and induce cellular apoptosis. In vivo, they demonstrate prolonged circulation in blood, induce no systemic toxicity, and show high potency in inhibiting tumor growth and metastasis in both mouse models of aggressive, drug-resistant breast cancer and melanoma. This study points to a new strategy toward improved anti-cancer drug delivery and therapy.2020-01-01T00:00:00Z2020 Sep2026-06-06T20:34:21.217Z2022-02-11T09:59:07.744ZS-EPMC79444053371654910.1016/j.mattod.2020.03.005