Targeted antitumor comparison study between dopamine self-polymerization and traditional synthesis for nanoparticle surface modification in drug delivery.

To improve the therapeutic efficacy of anticancer agents and extend their application, mussel-inspired chemical modifications have attracted considerable attention. Surface modification based on polydopamine (PDA) has been a facile and versatile method to immobilize biomolecules on substrates for targeted drug delivery. To better analyze pharmaceutical differences between PDA-based surface modification and traditional synthesis methods, we prepared two kinds of folate (FA)-targeted nanoparticles (NPs) loaded with paclitaxel (PTX). The resultant PTX-PDA-FA NPs and PTX-FA NPs represented PDA and synthesis strategies, respectively. PTX-PDA-FA NPs and PTX-FA NPs have been characterized. The particle size of PTX-PDA-FA NPs was smaller than that of PTX-FA NPs. The two kinds of NPs both exhibited long-rod morphology, good colloidal stability and sustained slow drug release. Cytotoxicityin vitrowas evaluated, and antitumor efficacy was investigated against 4T1 tumor-bearing mice. The tumor targeting therapeutic index of PTX-PDA-FA NPs and PTX-FA NPs showed equivalent superior specificity compared to nontargeted groups, which indicated that FA successfully attached to the surface of NPs by the PDA method and that the antitumor effect was equivalent to that of FA-modified NPs prepared by the chemical synthesis method. These results further indicated that PDA, as a simple and effective chemical surface modification platform, could be developed and applied in targeted delivery systems.

Photothermal combined with intratumoral injection of annonaceous acetogenin nanoparticles for breast cancer therapy.

ACGs (annonaceous acetogenins) possess excellent antitumor activity, but their serious accompanying toxicity has prevented their application in the clinic. To address this problem, we therefore constructed an intratumoral drug delivery system integrating chemotherapy and photothermal therapy. The PEGylation of polydopamine nanoparticles (PDA-PEG NPs) possessed an excellent biocompatibility with size of 70.96 ± 2.55 nm, thus can be used as good photothermal materials in the body. Moreover, PDA-PEG NPs can kill half of cancer cells under NIR (near-infrared) laser irradiation, and the survival rate of 4T1 cells is only 1% when ACG NPs and PDA-PEG NPs are combined. In vivo distribution studies showed that the 0.1 mg/kg ACGs NPs + PDA-PEG NPs + NIR group had the highest tumor inhibition rate, which was significantly superior to that of the 0.1 mg/kg ACGs NPs intratumoral injection group (82.65% vs. 59.08%). Altogether, the combination of PDA-PEG NPs + NIR with chemotherapy drugs may provide a feasible and effective strategy for the treatment of superficial tumors.

Combined Photothermal Therapy and Lycium barbarum Polysaccharide for Topical Administration to Improve the Efficacy of Doxorubicin in the Treatment of Breast Cancer.

In order to improve the efficacy of doxorubicin in the treatment of breast cancer, we constructed a drug delivery system combined with local administration of Lycium barbarum polysaccharides (LBP) and photothermal-material polypyrrole nanoparticles (PPY NPs). In vitro cytotoxicity experiments showed that the inhibitory effect of DOX + LBP + PPY NPs on 4T1 cells under NIR (near infrared) laser was eight times that of DOX at the same concentration (64% vs. 8%). In vivo antitumor experiments showed that the tumor inhibition rate of LBP + DOX + PPY NPs + NIR reached 87.86%. The results of the H&E staining and biochemical assays showed that the systemic toxicity of LBP + DOX + PPY NPs + NIR group was reduced, and liver damage was significantly lower in the combined topical administration group (ALT 54 ± 14.44 vs. 28 ± 3.56; AST 158 ± 16.39 vs. 111 ± 20.85) (p < 0.05). The results of the Elisa assay showed that LBP + DOX + PPY NPs + NIR can enhance efficacy and reduce toxicity (IL-10, IFN-γ, TNF-α, IgA, ROS). In conclusion, LBP + DOX + PPY NPs combined with photothermal therapy can improve the therapeutic effect of DOX on breast cancer and reduce its toxic side effects.