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Enhanced cell uptake of fluorescent drug-loaded nanoparticles via an implantable photothermal fibrous patch for more effective cancer cell killing.

ABSTRACT: Great efforts have been devoted to effective delivery of therapeutics into cells for cancer therapy. The exploration of nanoparticle based drug delivery systems (DDSs) faces daunting challenges in low efficacy of intracellular delivery. Herein, a localized drug delivery device consisting of photoluminescent mesoporous silica nanoparticles (PLMSNs) and photothermal fibrous matrix was investigated. Specifically, PLMSNs modified with a pH-sensitive polydopamine (PDA) 'gatekeeper' served as a doxorubicin (DOX) carrier and could release DOX once the PLMSNs were up-taken by the cancer cells. The PLMSNs were electrostatically assembled on the surface of electrospun biodegradable poly(?-caprolactone)/gelatin fibrous mesh incorporated with photothermal carbon nanoparticles (CNPs), leading to an implantable patch used as localized delivery platform. Comparing to free particulate DDSs, this implantable composite patch device was found to significantly enable superior cell up-taking effect and consequently enhance in-vitro therapeutic efficacy against tumor cells. Namely, under near infrared irradiation, the photothermal effect of CNPs in the implantable patch weakens the electrostatic interaction between the PLMSNs and poly(?-caprolactone)/gelatin/CNP fibrous mesh, resulting in the controlled release of the PLMSNs and subsequent internalization into the tumor cells for more effective cancer cell killing. This implantable therapeutic device may therefore inspire another way of developing localized cancer therapy.

SUBMITTER: Li Y

PROVIDER: S-EPMC5730969 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Enhanced cell uptake of fluorescent drug-loaded nanoparticles via an implantable photothermal fibrous patch for more effective cancer cell killing.

Li Yangyang Y Fu Yike Y Ren Zhaohui Z Li Xiang X Mao Chuanbin C Han Gaorong G

Journal of materials chemistry. B 20170907 36

Great efforts have been devoted to effective delivery of therapeutics into cells for cancer therapy. The exploration of nanoparticle based drug delivery systems (DDSs) faces daunting challenges in low efficacy of intracellular delivery. Herein, a localized drug delivery device consisting of photoluminescent mesoporous silica nanoparticles (PLMSNs) and photothermal fibrous matrix was investigated. Specifically, PLMSNs modified with a pH-sensitive polydopamine (PDA) 'gatekeeper' served as a doxoru ...[more]

PMID: 29255606

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Project description:Resistance to conventional antibiotics is a growing public health concern that is quickly outpacing the development of new antibiotics. This has led the Infectious Diseases Society of America (IDSA) to designate Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species as "ESKAPE pathogens" on the basis of the rapidly decreasing availability of useful antibiotics. This emphasizes the urgent need for alternative therapeutic strategies to combat infections caused by these and other bacterial pathogens. In this study, we used Staphylococcus aureus (S. aureus) as a proof-of-principle ESKAPE pathogen to demonstrate that an appropriate antibiotic (daptomycin) can be incorporated into polydopamine-coated gold nanocages (AuNC@PDA) and that daptomycin-loaded AuNC@PDA can be conjugated to antibodies targeting a species-specific surface protein (staphylococcal protein A; Spa) as a means of achieving selective delivery of the nanoconstructs directly to the bacterial cell surface. Targeting specificity was confirmed by demonstrating a lack of binding to mammalian cells, reduced photothermal and antibiotic killing of the Spa-negative species Staphylococcus epidermidis, and reduced killing of S. aureus in the presence of unconjugated anti-Spa antibodies. We demonstrate that laser irradiation at levels within the current safety standard for use in humans can be used to achieve both a lethal photothermal effect and controlled release of the antibiotic, thus resulting in a degree of therapeutic synergy capable of eradicating viable S. aureus cells. The system was validated using planktonic bacterial cultures of both methicillin-sensitive and methicillin-resistant S. aureus strains and subsequently shown to be effective in the context of an established biofilm, thus indicating that this approach could be used to facilitate the effective treatment of intrinsically resistant biofilm infections.

Dataset Information

Enhanced cell uptake of fluorescent drug-loaded nanoparticles via an implantable photothermal fibrous patch for more effective cancer cell killing.

Publications

Enhanced cell uptake of fluorescent drug-loaded nanoparticles via an implantable photothermal fibrous patch for more effective cancer cell killing.

Similar Datasets

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