Gold Nanorods Functionalized with Cathepsin B Targeting Peptide and Doxorubicin for Combinatorial Therapy against Multidrug Resistance

Abstract

Multidrug resistance (MDR) and adverse effects of chemotherapeutic agents are severe issues in clinical cancer treatment. Due to the dysregulation of enzymes in the cancer cells, enzyme-responsive drug delivery systems (DDSs) have been considered as a viable technology for cancer chemotherapy. In the present work, doxorubicin (DOX) is visible after leaving from AuNR–LAX. After treatment with AuNR–LAX, the drug resistance index of DOX-resistant MCF-7/ADR cells was reduced from extremely high 955.0 to 1.7, implying high potential of AuNR–LAX in the MDR phenotype cancer treatment. In addition, the cellular viability of both MCF-7 and MCF-7/ADR cells decreased from 50% to 80% after treatment with AuNR–LAX along (equivalent DOX concentration = 2.3 μg/mL, Au concentration = 30 μg/mL) to below 10% after AuNR–LAX treatment plus radiation of 808 nm, due to the NIR photothermal effect of AuNRs. Human bronchial epithelial cell line 16HBE was chosen to evaluate the adverse effect of AuNR–LAX on the normal cells. At the low concentration, the cytotoxicity of LAX and AuNR–LAX is comparable for breast cancer cell MCF-7 and normal cell 16HBE. It is noted that, at high concentration (with equivalent DOX concentration = 13.1 μg/mL, Au concentration = 167.7 μg/mL), the cellular viability of 16HBE cells is over 50%, whereas that of MCF-7 cancer cells is close to 0, implying the potential of AuNR–LAX in reducing the adverse effects of DOX against normal cells/tissues. Overall, AuNR–LAX showed high potential in overcoming MDR and alleviating adverse effect on normal cells.

NIR/pH Dual-Responsive DOX-Loaded AuNRs@S-β-CD Nanocomposite for Highly Effective Chemo-photothermal Synergistic Therapy against Lung Cancer Cells

“…Combination therapy with multiple treatments is more efficient than single therapy because it decreases drug-induced toxicity, creates synergistic anticancer effects, and inhibits multidrug resistance via different mechanisms. 19 Therefore, the use of two methods or different types of methods of treatment or a method to boost another method of treatment has developed a new trend in cancer treatment. 20 The combination of chemotherapy and photothermal therapy can be more effective than single therapy because hyperthermia was exhibited to result in higher and faster drug release into a tumor, 21 and improvement of the anticancer effect of chemotherapeutic drugs such as doxorubicin.…”

“…In recent years, many researchers have paid attention to the tumor targeted combination therapies, particularly in the field of nanomedicine. Combination therapy with multiple treatments is more efficient than single therapy because it decreases drug-induced toxicity, creates synergistic anticancer effects, and inhibits multidrug resistance via different mechanisms . Therefore, the use of two methods or different types of methods of treatment or a method to boost another method of treatment has developed a new trend in cancer treatment .…”

Recent advances in peptide-based therapeutic strategies for breast cancer treatment

“…In these PKC-pseudosubstrate peptides, P1 revealed the most likely reversing MDR mechanism of inhibition of P-gp phosphorylation ( Gupta et al, 1996 ). Zhi et al designed a novel compound, LAX, composed of tetrapeptide (GFLG), DOX and lipoid acid ( Zhi et al, 2019 ), in which tetrapeptide was a trigger of lysosomal protease cathepsin B existing inside most tumor cells ( Li et al, 2014 ). They selected gold nanorods (AuNRs) as a vector to deliver LAX to form an enzyme-responsive nanomedicine AuNRs-LAX.…”

Recent Progress of Novel Nanotechnology Challenging the Multidrug Resistance of Cancer

“…For approaching the accurate and rapid drug release, reduced toxic side effects, and increased intercellular drug concentration, some tumor microenvironment physiological properties which are different from those of normal tissues, such as pH and enzyme concentration ( Llopis-Lorente et al, 2019 ; Gannimani et al, 2020 ), have been widely utilized as environmental stimuli for triggering the drug release of NDDSs, and tremendous studies have emerged continuously in recent years ( Zhang C. et al, 2017 ; Che et al, 2019 ; Liu Z. et al, 2019 ; Zhi et al, 2019 ; Wang J. et al, 2020 ; Kumar et al, 2020 ; Luo et al, 2020 ; Mei et al, 2020 ).…”