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

Abstract

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(ε-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.

An Innovative Polymeric Platform for Controlled and Localized Drug Delivery

“…The two biocompatible polymers used in this study were polycaprolactone (PCL) and polylactic acid (PLA), which were mixed with RhB to form the PCRS devices. The PCL was approved by the Food and Drug Administration (FDA) to be utilized as an implantable device due to its high biocompatibility and harmless biodegradation [ 28 , 29 , 30 ]. It was selected due to its melting point of 60 °C, malleability, and capacity to be 3D printed [ 31 , 32 , 33 ].…”

Recent Advances in Nanotechnology-Based Targeted Delivery Systems of Active Constituents in Natural Medicines for Cancer Treatment

“…[36,38,39]; (2) hydrophobic polymers, such as poly lactic-co-glycolic acid (PLGA), polycaprolactone (PCL), polylactic acid (PLA), etc. [36,[40][41][42]; (3) amphiphilic block copolymers, mainly including D-alphatocopheryl polyethylene glycol succinate (TPGS), Soluplus ® , and Pluronic ® (F127, F68, and P123) [13,[43][44][45][46][47][48][49]. The classification and structures of the aforementioned polymers are shown in Table 1.…”

“…Poly lactic-co-glycolic acid (PLGA) [35,41] Polycaprolactone (PCL) [42,53] Polylactic acid (PLA) [34,40] Amphiphilic block copolymers D-alpha-tocopheryl polyethylene glycol succinate (TPGS) [43,44] Soluplus ® [47] Pluronic ® (F127, F68, P123) [45,46,49,54] [ 34,40] Amphiphilic block copolymers D-alpha-tocopheryl polyethylene glycol succinate (TPGS)…”

“…Poly lactic-co-glycolic acid (PLGA) [35,41] Polycaprolactone (PCL) [42,53] Polylactic acid (PLA) [34,40] Amphiphilic block copolymers D-alpha-tocopheryl polyethylene glycol succinate (TPGS) [43,44] Soluplus ® [47] Pluronic ® (F127, F68, P123) [45,46,49,54] Molecules 2023, 28, 7767 6 of 34 particle size was 124.3 ± 6.4 nm and could remain stable even after 15 days stored at 4 °C. ADGloaded micelles had more outstanding anti-tumor ability and higher bioavailability compared to free ADG.…”

“…Poly lactic-co-glycolic acid (PLGA) [35,41] Polycaprolactone (PCL) [42,53] Polylactic acid (PLA) [34,40] Amphiphilic block copolymers D-alpha-tocopheryl polyethylene glycol succinate (TPGS) [43,44] Soluplus ® [47] Pluronic ® (F127, F68, P123) [45,46,49,54] [ 45,46,49,54] Polymer-mixed micelles (PMMs), formed by two or more different types of copolymers, can eliminate complex synthesis schemes of carrier materials, improve the stability of nanomicelles, enhance the compatibilization of hydrophobic compounds, and increase the anti-tumor efficacy of drugs [47,55]. In addition, PMMs have a smaller particle size (usually less than 100 nm), which is more conducive to cellular uptake and is a promising drug delivery system [55,56].…”