Near IR responsive targeted integrated lipid polymer nanoconstruct for enhanced magnolol cytotoxicity in breast cancer

Abstract

Advances in cancer nanotechnology aim at improving specificity and effectiveness for tumor treatment. Amalgamation of different treatment modalities is expected to provide better cancer combating. Herein, We developed a long circulating nanocarrier comprising trastuzumab (TZB) surface modified polylactic-co-glycolic acid (pLGA) nanoparticles (nps) co-encapsulating magnolol (Mag) and gold nanoparticles (GNPs). A modified single step nanoprecipitation method was adopted ensuring particle coating with D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) while co-encapsulating Gnps. tZB was then anchored on nps surface using a carbodiimide chemistry. the cytotoxicity of the developed system was evaluated with and without photothermal irradiation. nps cellular uptake was then followed using confocal microscopical imaging. A hybrid matrix composed of pLGA/tpGS and surface decorated with TZB with a conjugation efficiency of ˃65%, was confirmed via ftiR, 1 HnMR. Gnps could only be included in the nps, when placed in the organic phase as evidenced by the shifted GNPs surface plasmonic resonance and confirmed via imaging coupled with energy dispersive X-ray analysis. Optimized NPs (136.1 ± 1.3 nm, −8.2 ± 1 mV and Mag encapsulation efficiency of 81.4 ± 1.8%) were able to boost Mag cytotoxicity on breast cancer cells while providing a selective multifunctional therapy with an added photothermal effect. Despite the great advances in cancer research, breast cancer remains one of the most challenging diseases risking the lives of a considerable proportion of women world wide 1. Lack of selectivity, poor drug penetration in solid tumors, multi drug resistance (MDR) with increased cells sensitivity added to the drug systemic side effects, represent some of the major barriers for a successful therapy 2. Smart drug delivery systems incorporating different cancer targeting approaches including: passive, active and stimuli responsive had been suggested to improve outcomes of cancer treatment 3,4. In this study, we focused on integrating many strategies that could potentiate the effect of a natural cytotoxic drug with potential activity against breast cancer. Magnolol (Mag), see structure Fig. S1, is a phenolic polyhydroxy compound isolated from the root and stem bark of Magnolia Officinalis 5. It had been found to inhibit proliferation and induce apoptosis in MCF-7 breast cancer cells via the intrinsic pathway with release of apoptosis inducing factor from mitochondria 5,6. Studies have also shown that Mag inhibited cell growth and HER2-mediated tumor metastasis in human HER2-cancer cells 7. Although, Mag might be considered a potential lead drug in breast cancer treatment yet, its delivery is usually hampered by poor aqueous solubility and low oral bioavailability 6,8. Hence, its incorporation in a smart nanocarrier is expected to improve its delivery characteristics and boost its anticancer properties especially with the incorporation of multifunctional adjuvants.

PEI‐PLGA nanoparticles significantly enhanced the immunogenicity of IsdB137‐361 proteins from Staphylococcus aureus

“…The results showed that the entrapment efficiency of MAG was over 81%, which improved the cytotoxicity of MAG to breast cancer cells and provided photothermal effect for multifunctional therapy of breast cancer cells. The encapsulated photothermal material GNPs enables the nano‐carrier to give near‐infrared photothermal response, which improves the cytotoxicity of drugs and enhances the specificity to cancer cells 38 . We thus hypothesized that targeting antigen present cells modification of IsdB 137‐361 ‐PEI‐PLGA nanoparticles might have a better immune effect, but this needs to be verified by subsequent experiments.…”

Tumor Microenvironment Regulation and Cancer Targeting Therapy Based on Nanoparticles

“…There have many reports about the use of hybrid NPs in cancer detection and treatment. There are some hybrid NPs for clinical diagnosis of cancer, including hybrid magnetic silicon dioxide NPs [ 137 ] and hybrid supermagnetic iron oxide NPs (SPIONS) [ 138 , 139 , 140 , 141 ]. Some hybrid NPs are used for cancer treatment, such as lipid coated polymers [ 142 , 143 ] and hybrid NPs coupled with genes [ 144 ].…”

“…Therefore, combining the advantages of the two to construct hybrid nanocarriers can not only improve the targeting ability of nanocarriers, but also increase the anti-tumor effect of drugs. For example, Elhabak’ team developed a trastuzumab (TZB) surface modified poly(lactic-co-glycolic) acid (PLGA), circulating NPs that co-encapsulated magnolol (Mag) and gold NPs [ 139 ]. The optimized NPs have small particle sizes and high encapsulation efficiency.…”

Role of Polyphenols and Flavonoids as Anti-Cancer Drug Candidates: A Review

“…[66] Together with magnolol and obovatol as analgesics, honokiol has been prescribed in conventional treatments to address depression and anxiety issues. [67] Multiple studies have discovered that honokiol has the capacity to destroy tumour cells in various types of cancer. [68][69][70]…”