Hybrid Clustered Nanoparticles for Chemo-Antibacterial Combinatorial Cancer Therapy

Abstract

Background: A great number of therapeutic limitations, such as chemoresistance, high dosage, and long treatments, are still present in cancer therapy, and are often followed by side effects such as infections, which represent the primary cause of death among patients. Methods: We report pH- and enzymatic-responsive hybrid clustered nanoparticles (HC-NPs), composed of a PCL polymeric core loaded with an anticancer drug, such as Imatinib Mesylate (IM), and coated with biodegradable multilayers embedded with antibacterial and anticancer baby-ship silver NPs, as well as a monoclonal antibody for specific targeting of cancer cells conjugated on the surface. Results: The HC-NPs presented an onion-like structure that serially responded to endogenous stimuli. After internalization into targeted cancer cells, the clustered nanoparticles were able to break up, thanks to intracellular proteases which degraded the biodegradable multilayers and allowed the release of the baby-ship NPs and the IM loaded within the pH-sensible polymer present inside the mothership core. In vitro studies validated the efficiency of HC-NPs in human chronic leukemic cells. This cellular model allowed us to demonstrate specificity and molecular targeting sensitivity, achieved by using a combinatorial approach inside a single nano-platform, instead of free administrations. The combinatory effect of chemotherapic drug and AgNPs in one single nanosystem showed an improved cell death efficacy. In addition, HC-NPs showed a good antibacterial capacity on Gram-negative and Gram-positive bacteria. Conclusions: This study shows an important combinatorial anticancer and antimicrobial effect in vitro.

Capsid-like biodegradable poly-glycolic acid nanoparticles for a long-time release of nucleic acid molecules

“…Hemolysis assays were performed as described in our previous work. 26 Briefly, different DNA-loaded PGA NP formulations and DNA-Lipofectamine 3000 were incubated with 2% mouse blood for 24 hours at 37 1C with shaking (600 rpm). After centrifugation to remove the NPs, the supernatant absorption at a wavelength of 540 nm was evaluated using a UV-visible spectrophotometer (Varian Cary s 300 Scan; Varian Instruments, CA, USA) and the hemolytic rate was calculated.…”

“…Recently, we have developed a versatile polymeric system for drug and gene delivery based on pH-responsive and enzymeresponsive core/shell NPs using the Food and Drug Administration (FDA) approved poly-caprolactone (PCL) polymer. [24][25][26][27] Another attractive polymer for therapeutic molecule delivery applications is poly-glycolic acid (PGA), which has been approved by the FDA. PGA, after degradation, can be excreted in the metabolism of the tricarboxylic acid cycle.…”

Intrinsic stimuli‐responsive nanocarriers for smart drug delivery of antibacterial agents—An in‐depth review of the last two decades

“…of enzyme-responsive nanocarriers of antibacterial agents (Baier et al, 2013;M. Chen, Xie, et al, 2018;Cortese et al, 2019;Li et al, 2016;Thamphiwatana et al, 2014;M. H. Xiong, Li, et al, 2012;Yang et al, 2018; T A B L E 3 Enzymes that have a biocatalytic action on nanomaterials for drug delivery in antibacterial applications Chen, Xie, et al (2018) Phosphatase and phospholipase Mannosyl Vancomycin M. H. Xiong, Li et al (2012) Phospholipase A 2 1,2-Distearoyl-sn-glycero-3-phosphocholine (DSPC) and 1,2-dioctadecanoyl-sn-glycero-3-phospho-(10-rac-glycerol) (sodium salt) (DSPG) Doxycycline Thamphiwatana et al (2014) Penicillin G amidase and β-lactamase Phenylacetic amide and cephalosporin, both affording poly (2-aminoethyl methacrylate) Scaffolds…”

Cancer Nanomedicine

“…With improved tumour retardation, reduced drug resistance and better patient prognosis. As such, nanomedicines are under development incorporating combination therapies [ 30 , 42 ] in the hope to further enhance the findings found in small molecule trials, with the protective capabilities of nanomedicines through targeting techniques in order to reduce the toxic side effects of the potent compounds attributed to systemic circulation.…”

“…As the science develops and leads us down new avenues, the findings and their meaning are closely scrutinised and debated within the community. This issue includes 32 scientific manuscripts, 13 review articles and 1 case report reflecting the hot topics within this area [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ].…”