title: 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.
abstract: 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 composite's 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 composite's 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.
authors.affiliation: †School of Chemistry and Chemical Engineering, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu 212013, China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Pan
authors.affiliation: †School of Chemistry and Chemical Engineering, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu 212013, China.
authors.forename: Runrun
authors.initials: R
authors.lastname: Wu
authors.affiliation: †School of Chemistry and Chemical Engineering, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu 212013, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Dai
authors.affiliation: †School of Chemistry and Chemical Engineering, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu 212013, China.
authors.forename: Yijie
authors.initials: Y
authors.lastname: Yin
authors.affiliation: ‡Orthopaedic Institute, Soochow University, 708 Renmin Road, Suzhou, Jiangsu 215007, China.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Pan
authors.affiliation: †School of Chemistry and Chemical Engineering, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu 212013, China.
authors.forename: Minjia
authors.initials: M
authors.lastname: Meng
authors.affiliation: †School of Chemistry and Chemical Engineering, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu 212013, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Shi
authors.affiliation: †School of Chemistry and Chemical Engineering, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu 212013, China.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Yan
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D053758:Nanoparticles / Q000737:chemistry*; D012822:Silicon Dioxide / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D000970:Antineoplastic Agents; D012822:Silicon Dioxide; D004317:Doxorubicin