<p>Enhancement of Pancreatic Cancer Therapy Efficacy by Type-1 Matrix Metalloproteinase-Functionalized Nanoparticles for the Selective Delivery of Gemcitabine and Erlotinib</p>

Abstract

Purpose Pancreatic cancer (PCa) is projected to become the second leading cause of cancer-related deaths by 2030. Gemcitabine (GEM) combined with erlotinib (ERL) have been approved by the FDA for locally advanced, unresectable or metastatic pancreatic cancer therapy since 2005. Type-1 matrix metalloproteinase (MT1-MMP) has been recognized as a critical mediator of several steps in PCa progression including activating TGF-β or releasing latent TGF-β from LTBP-1, resulting in increased collagen production and cleavage collagen. Methods In the present research, GEM and ERL co-loaded nanoparticles (GEM/ERL NPs) were prepared. A non-substrate MT1-MMP binding peptide was decorated onto the GEM/ERL NPs surface. Results M-M GEM/ERL NPs exhibited the highest uptake ability (67.65 ± 2.87%), longest half-life period, largest area under the curve, and the best tumor inhibition efficiency (69.81 ± 4.13%). The body weight, blood urine nitrogen (BUN), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) of the system were steady when tested in mice model. Conclusion In conclusion, M-M GEM/ERL NPs protected the drugs in the plasma, improved cellular uptake capacity, exhibited the most remarkable tumor cell inhibition ability, and showed the most efficient tumor growth inhibition capacity in vivo. M-M GEM/ERL NPs could be applied as an efficient and safe system for the synergistic combination chemotherapy of PCa.

Combination prostate cancer therapy: Prostate-specific membranes antigen targeted, pH-sensitive nanoparticles loaded with doxorubicin and tanshinone

“…N-DOX/TAN also presented more inhibition effect on tumor growth than N-DOX and N-TAN, which is consistent with the previous in vitro cytotoxicity and synergistic results and successfully highlighting the advantages of combing the DOX and TAN in one system for the PCa treatment as also illustrated by Yin et al. ( 2020 ). Bodyweight variations and other parameters were calculated to evaluate the systemic toxicity of different systems (Cui et al., 2017 ).…”

Passing of Nanocarriers across the Histohematic Barriers: Current Approaches for Tumor Theranostics

“…In tumors such as pancreatic cancer, a critical role in drug delivery having the ability of NPs to pass through the dense extracellular matrix (ECM), which consists of such branching molecules as collagen, fibronectin, proteoglycan, and hyaluronic acid [ 114 ]. Thus, the conjugation of NPs with ECM enzymes such as hyaluronidase, collagenase, and matrix metalloproteinases (MMPs) is considered a bioavailability enhancer of main drugs in the therapy of pancreatic and breast cancers [ 115 , 116 , 117 ]. The straightforward composition of NPs, containing molecules such as hyaluronidase, results in the fast inactivation and biodegradation of NPs due to the serum proteins in blood flow.…”

Nanotechnology and Matrix Metalloproteinases in Cancer Diagnosis and Treatment

“…Nanocarriers for drug delivery have been used instead of free chemotherapeutic agents. In this context, the combination of gemcitabine (GEM) and erlotinib (ERL) conjugated to NPs was used in vitro and in vivo assays to treat pancreatic cancer ( Yin et al, 2020 ). Briefly, GEM/ERL was bound to PEG-DSPE-maleimide to construct the GEM/ERL-PEG-DSPE-maleimide NPs.…”