Doxorubicin-loaded protease-activated near-infrared fluorescent polymeric nanoparticles for imaging and therapy of cancer

Abstract

IntroductionDespite significant progress in the field of oncology, cancer remains one of the leading causes of death. Chemotherapy is one of the most common treatment options for cancer patients but is well known to result in off-target toxicity. Theranostic nanomedicines that integrate diagnostic and therapeutic functions within an all-in-one platform can increase tumor selectivity for more effective chemotherapy and aid in diagnosis and monitoring of therapeutic responses.Material and methodsIn this work, theranostic nanoparticles were synthesized with commonly used biocompatible and biodegradable polymers and used as cancer contrast and therapeutic agents for optical imaging and treatment of breast cancer. These core–shell nanoparticles were prepared by nanoprecipitation of blends of the biodegradable and biocompatible amphiphilic copolymers poly(lactic-co-glycolic acid)-b-poly-l-lysine and poly(lactic acid)-b-poly(ethylene glycol). Poly-l-lysine in the first copolymer was covalently decorated with near-infrared fluorescent Alexa Fluor 750 molecules.ResultsThe spherical nanoparticles had an average size of 60–80 nm. The chemotherapeutic drug doxorubicin was encapsulated in the core of nanoparticles at a loading of 3% (w:w) and controllably released over a period of 30 days. A 33-fold increase in near-infrared fluorescence, mediated by protease-mediated cleavage of the Alexa Fluor 750-labeled poly-l-lysine on the surface of the nanoparticles, was observed upon interaction with the model protease trypsin. The cytocompatibility of drug-free nanoparticles and growth inhibition of drug-loaded nanoparticles on MDA-MB-231 breast cancer cells were investigated with a luminescence cell-viability assay. Drug-free nanoparticles were found to cause minimal toxicity, even at high concentrations (0.2–2,000 µg/mL), while doxorubicin-loaded nanoparticles significantly reduced cell viability at drug concentrations >10 µM. Finally, the interaction of the nanoparticles with breast cancer cells was studied utilizing fluorescence microscopy, demonstrating the potential of the nanoparticles to act as near-infrared fluorescence optical imaging agents and drug-delivery carriers.ConclusionDoxorubicin-loaded, enzymatically activatable nanoparticles of less than 100 nm were prepared successfully by nanoprecipitation of copolymer blends. These nanoparticles were found to be suitable as controlled drug delivery systems and contrast agents for imaging of cancer cells.

Preparation of PLGA-chitosan based nanocarriers for enhancing antibacterial effect of ciprofloxacin in root canal infection

“…The bands of the symmetric stretching are present between 2850 and 2980 cm À1, while the band of asymmetric stretching for CH3 is 1375 cm À1 and CH2 is 1450 cm À1 . The band at 1760 cm À1 caused by the C¼O bond stretching of the esters (Yildiz et al, 2018). The 1110 cm À1 and the 1185 cm À1 are found to be bands relative to the C-O stretching of aliphatic polyesters this is in consistence with Yildiz et al (2018) who stated that alkyl C -H stretch peak at 2950-2850 cm À1 , ester C¼O stretch peak at 1750-1735 cm À1 , and C -O-C stretch peak at 1250-1050 cm À1 , respectively.…”

“…The band at 1760 cm À1 caused by the C¼O bond stretching of the esters (Yildiz et al, 2018). The 1110 cm À1 and the 1185 cm À1 are found to be bands relative to the C-O stretching of aliphatic polyesters this is in consistence with Yildiz et al (2018) who stated that alkyl C -H stretch peak at 2950-2850 cm À1 , ester C¼O stretch peak at 1750-1735 cm À1 , and C -O-C stretch peak at 1250-1050 cm À1 , respectively. The drug spectra in F2 and F3 shows the attenuated peaks of the drug, the main characteristic peaks are a broad peak between 3400 and 3500 cm À1 indicates OH stretching vibration (intermolecular hydrogen bonding) and the peaks between 1600 and 1650 cm À1 was assigned to quinolones and they are present in F2 and F3, this is in agreement with many reports (Tom et al, 2004;Sahoo et al, 2011).…”

Nanoparticle Activation Methods in Cancer Treatment

“…The structure change releases the entrapped drugs and can be reversible or irreversible depending on the polymers used. The second method involves the application of a permanent magnetic field, causing the IONs to drag and squeeze the liposomes to a point at which they burst and the payload is released [43,95,96,97,98]. Nanocapsules designed in this manner by an emulsion approach have enabled the simultaneous activated delivery of both hydrophobic and hydrophilic drug molecules contained within the same vesicle.…”

“…The copolymers were conjugated to a NIR fluorophore and used to image tumour tissue non-invasively at the same time as carrying a cytotoxic drug to tumour tissues. The drug was released after the copolymer was biodegraded by the high concentration of lysosomal cathepsins in cancer cells [43].…”

Application of Nanomaterials in Biomedical Imaging and Cancer Therapy

“…DOX was encapsulated in the core of the NPs. The results showed a 33-fold increase in NIR fluorescence in the mouse model and found it to be suitable for a controlled drug delivery system and a contrast agent for imaging cancer cells [ 208 ]. PTT in combination with chemotherapy can trigger powerful antitumour immunity against tumours.…”