Yijie Yin

A Hierarchical Porous Bowl-like PLA@MSNs-COOH Composite for pH-Dominated Long-Term Controlled Release of Doxorubicin and Integrated Nanoparticle for Potential Second Treatment

We chemically integrated mesoporous silica nanoparticles (MSNs) and macroporous bowl-like polylactic acid (pBPLA) matrix, for noninvasive electrostatic loading and long-term controlled doxorubicin (DOX) release, to prepare a hierarchical porous bowl-like pBPLA@MSNs-COOH composite with a nonspherical and hierarchical porous structure. Strong electrostatic interaction with DOX rendered excellent encapsulation efficiency (up to 90.14%) to the composite. DOX release showed pH-dominated drug release kinetics; thus, maintaining a weak acidic pH (e.g., 5.0) triggered sustained release, suggesting the composites great potential for long-term therapeutic approaches. In-vitro cell viability assays further confirmed that the composite was biocompatible and that the loaded drugs were pharmacologically active, exhibiting dosage-dependent cytotoxicity. Additionally, a wound-healing assay revealed the composites intrinsic ability to inhibit cell migration. Moreover, pH- and time-dependent leaching of the integrated MSNs due to pBPLA matrix degradation allow us to infer that the leached (and drug loaded) MSNs may be engulfed by cancer cells contributing to a second wave of DOX-mediated cytotoxicity following pH-triggered DOX release.

A traceable porous bowl-like PLA@C-dots composite for in vitro drug delivery system: A case study of artemisinin.

Due to its excellent biocompatibility and biodegradability, poly(lactic acid) (PLA) has been extensively studied for controlled drug release [1]. Most of PLA-based drug delivery systems are spherical capsules or particles. However, recent studies have proven that non-spherical particles may be optimal for in vivo drug release [2]. Carbon dots (Cdots) as emerging bio-nontoxic luminescent materials have been extensively studied in target tracing. Artemisinin (ART) has special antitumor activity against melanoma, ovarian, breast, prostate, central nervous system, and renal cancer cell lines. However, it suffers many drawbacks such as low bio-availability, easy decomposition and high hydrophobicity. Herein, we have successfully produced a novel traceable porous bowl-like PLA@C-dots (TPBL-PLA@C-dots) composite, which can load ART through hydrogen bonding. The TPBL-PLA@C-dots composites were prepared by a modified emulsion-solvent evaporation method through electrostatic interaction of de-wetting process, a hydrolysis process and covalently bonding of C-dots afterwards (Fig. 1). The average size of TPBLPLA@C-dots and carbon dots were 8.0 μm and 4.0 nm, respectively, and they both exhibited strong luminescent under a 365 nm UV lamp. The loading efficiency of TPBL-PLA@C-dots was calculated to be as high as 169.26 μmol/g, and the ART was released in a sustained way. The as-prepared TPBL-PLA@C-dots composites with superior stability, reasonable drug loading and sustained release are promising for cancer chemotherapy.