Wang, Shanfeng

To satisfy different mechanical requirements in hard and soft tissue replacements, a series of biodegradable and crosslinkable copolymers of poly(propylene fumarate)‐co‐polycaprolactone (PPF‐co‐PCL) are synthesized and employed to fabricate 2D disks and 3D scaffolds via photocrosslinking. Thermal properties such as the glass transition temperature (Tg) and melting temperature (Tm) of the PPF‐co‐PCL networks can be controlled efficiently by varying the PCL composition (φPCL). As a result, their mechanical properties vary significantly from hard and stiff materials to soft and flexible ones with increasing φPCL, making them attractive candidate materials for bone and peripheral nerve regeneration, respectively. Several PPF‐co‐PCL formulations are selected to perform in vitro cell studies using mouse pre‐osteoblastic MC3T3‐E1, rat Schwann cell precursor line (SPL201), and pheochromocytoma (PC12) cells, and in vivo animal testing in the rat femur bone defect model and in the rat sciatic nerve transection model. The formation of new bone in the porous bone scaffolds with a low φPCL and guided axon growth through the nerve conduits with a higher φPCL suggest that crosslinked PPF‐co‐PCLs have appropriate compatibility and functionality. Furthermore, the role of surface stiffness in modulating cellular behavior and functions is verified on the crosslinked PPF‐co‐PCL surfaces without any pretreatments.

Abstract One of the key challenges in anticancer therapy is the toxicity and poor bioavailability of the anticancer drugs. Nanotechnology can play a pivotal role by delivering drugs in a targeted fashion to the malignant cells that will reduce the systemic toxicity of the anticancer drug. In this report, we show a stepwise development of a nanoparticle-based targeted delivery system for in vitro and in vivo therapeutic application in pancreatic cancer. In the first part of the study, we have shown the fabrication and characterization of the delivery system containing gold nanoparticle as a delivery vehicle, cetuximab as a targeting agent, and gemcitabine as an anticancer drug for in vitro application. Nanoconjugate was first characterized physico-chemically. In vitro targeting efficacy, tested against three pancreatic cancer cell lines (PANC-1, AsPC-1, and MIA Paca2) with variable epidermal growth factor receptor (EGFR) expression, showed that gold uptake correlated with EGFR expression. In the second part, we showed the in vivo therapeutic efficacy of the targeted delivery system. Administration of this targeted delivery system resulted in significant inhibition of pancreatic tumor cell proliferation in vitro and orthotopic pancreatic tumor growth in vivo. Tumor progression was monitored noninvasively by measuring bioluminescence of the implanted tumor cells. Pharmacokinetic experiments along with the quantitation of gold both in vitro and in vivo further confirmed that the inhibition of tumor growth was due to targeted delivery. This strategy could be used as a generalized approach for the treatment of a variety of cancers characterized by overexpression of EGFR. [Cancer Res 2008;68(6):1970–8]