4.7 Article

Nanomicelle-Microsphere Composite as a Drug Carrier to Improve Lung-Targeting Specificity for Lung Cancer

Journal

PHARMACEUTICS
Volume 14, Issue 3, Pages -

Publisher

MDPI
DOI: 10.3390/pharmaceutics14030510

Keywords

micelles; microsphere; polyamine transport system; targeted drug delivery system; lung cancer

Funding

  1. University Natural Science Research Project of Anhui Province [KJ2020A0157]
  2. Key Laboratory of Xin'an Medicine Open Project Fund (Anhui University of Chinese Medicine), Ministry of Education [2020xayx02]
  3. National Natural Science Foundation of China [81973488]

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A nanomicelle-microsphere composite was developed for targeted treatment of lung cancer. The complex showed promising anti-tumor effects and targeted distribution in both in vitro and in vivo studies.
Lung cancer is the second-most common cancer and has the highest mortality among all cancer types. Nanoparticle (NP) drug delivery systems have been used to improve the therapeutic effectiveness of lung cancer, but rapid clearance and poor targeting limit their clinical utility. Here, we developed a nanomicelle-microsphere composite, in which doxorubicin (DOX) was loaded with spermine (Spm) modified poly (ethylene glycol)-poly(epsilon-caprolactone) (PEG-PCL) micelles, and then the nanomicelles were noncovalently adsorbed on the surface of poly (lactic-co-glycolic acid) (PLGA) microspheres. The attachment was confirmed by scanning electron microscopy and confocal microscopy. In vitro cell experiments, MTT assays and intracellular uptake assays were used to demonstrate the cytotoxicity and the cellular uptake of micelles in A549 cells. In vivo biodistribution studies were conducted, an orthotopic lung cancer implantation model based on C57BL/6 mice was established, and then real-time fluorescence imaging analysis was used to study the targeted efficacy of the complex. A nanomicelle-microsphere composite was successively constructed. Moreover, Spm-modified micelles significantly enhanced cytotoxicity and displayed more efficient cellular uptake. Notably, an orthotopic lung cancer implantation model based on C57BL/6 mice was also successively established, and in vivo biodistribution studies confirmed that the complex greatly improved the distribution of DOX in the lungs and displayed notable tumor targeting. These results suggested that the nanomicelle-microsphere composite has potential application prospects in the targeted treatment of lung cancer.

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