Improved antitumor activity through a tyramidyl maslinic acid derivative. Design and validation as drug-loaded electrospun polymeric nanofibers.

Among the most harmful tumors detected in the human body, such as breast, colon, brain or pancreas, breast (BC) and colorectal cancer (CRC) are the first and third most frequent cancer worldwide, respectively. The current existing chemotherapeutic treatments present serious side effects due to their intravenous administration can induce cytotoxicity in healthy cells. Thus, new treatment methods based on drug-loaded polymeric nanofibers (NFs) have gained significant potential for their use in localized cancer chemotherapy. Here, a deep in vitro comparative analysis between maslinic acid (MA) and a tyramine-maslinic acid (TMA) derivative is initially performed. This analysis includes a proliferation, and a cell cycle assay, and a genotoxicity, antiangiogenic and apoptosis study. Then, the TMA derivative has been incorporated into electrospun polymeric NFs obtaining an implantable dressing material with antitumor activity. Two types of patches containing TMA-loaded polymeric NFs of poly(caprolactone) (PCL), and a mixture of polylactic acid/poly(4-vinylpyridine) (PLA/PVP) were fabricated by the electrospinning technique. The characterization of the drug-loaded NFs showed an encapsulation capacity of 0.027 mg TMA/mg PCL and 0.024 mg TMA/mg PLA/PVP. Then, the cytotoxic activity of both polymeric systems was tested in CRC (T84), BC (MCF-7) and a no tumor (L929) cell lines exposed to TMA-loaded NFs and blank NFs for 48 h. Moreover, cell cycle assay, genotoxicity, angiogenesis and apoptosis tests were carried out to study the mechanism of action of TMA. Blank NFs showed no-toxicity in all cell lines tested and both drug-loaded NFs significantly reduced cell proliferation (relative proliferation of ≈44 % and ≈25 % respectively). Therefore, TMA was less genotoxic than maslinic acid (MA), and reduced VEGFA expression in MCF-7 cells (1.32 and 2.12-fold for MA and TMA respectively). These results showed that TMA-loaded NFs could constitute a promising biocompatible and biodegradable nanoplatform for the local treatment of solid tumors such as CRC or BC.

Temperature-Controlled Catalysis by Core-Shell-Satellite AuAg@pNIPAM@Ag Hybrid Microgels: A Highly Efficient Catalytic Thermoresponsive Nanoreactor.

A novel wet-chemical protocol is reported for the synthesis of "temperature-programmable" catalytic colloids consisting of bimetallic core@shell AuAg nanoparticles encapsulated into poly(N-isopropylacrylamide) (pNIPAM) microgels with silver satellites (AgSTs) incorporated within the microgel structure. Spherical AuNPs of 50 nm in diameter are initially synthesized and used for growing a pNIPAM microgel shell with temperature stimulus response. A silver shell is subsequently grown on the Au core by diffusing Ag salt through the hydrophilic pNIPAM microgel (AuAg@pNIPAM microgel). The use of allylamine as a co-monomer during pNIPAM polymerization facilitates the coordination of Ag+ with the NH2 nitrogen lone pair of electrons, which are reduced to Ag seeds (∼14 nm) using a strong reducing agent, obtaining thus AuAg@pNIPAM@Ag hybrid microgels. The two systems are tested as catalysts toward the reduction of 4-nitrophenol (4-Nip) to 4-aminophenol (4-Amp) by NaBH4. Both exhibit extremely sensitive temperature-dependent reaction rate constants, with the highest K1 value of the order of 0.6 L/m2 s, which is one of the highest values ever reported. The presence of plasmonic entities is confirmed by UV-vis spectroscopy. Dynamic light scattering proves the temperature responsiveness in all cases. Transmission electron microscopy and energy-dispersive X-ray (EDX) elemental mapping highlight the monodispersity of the synthesized hybrid nanostructured microgels, as well as their size and metallic composition. The amount of gold and silver in both systems is obtained by thermogravimetric analysis and the EDX spectrum. The reduction reaction kinetics is monitored by UV-vis spectroscopy at different temperatures for both catalytic systems, with the AuAg@pNIPAM@Ag microgels showing superior catalytic performance at all temperatures because of the synergistic effect of the AuAg core and the AgSTs. The principal novelty of this study lies in the "hierarchical" design of the metal-polymer-metal core@shell@satellite nanostructured colloids exhibiting synergistic capabilities of the plasmonic NPs for, among others, temperature-controlled catalytic applications.