In many organic reactions, the O(2) activation process involves a key step where inert ground triplet O(2) is excited to produce highly reactive singlet O(2). It remains elusive what factor induces the change in the electron spin state of O(2) molecules, although it has been discovered that the presence of noble metal nanoparticles can promote the generation of singlet O(2). In this work, we first demonstrate that surface facet is a key parameter to modulate the O(2) activation process on metal nanocrystals, by employing single-facet Pd nanocrystals as a model system. The experimental measurements clearly show that singlet O(2) is preferentially formed on {100} facets. The simulations further elucidate that the chemisorption of O(2) to the {100} facets can induce a spin-flip process in the O(2) molecules, which is achieved via electron transfer from Pd surface to O(2). With the capability of tuning O(2) activation, we have been able to further implement the {100}-faceted nanocubes in glucose oxidation. It is anticipated that this study will open a door to designing noble metal nanocatalysts for O(2) activation and organic oxidation. Another perspective of this work would be the controllability in tailoring the cancer treatment materials for high (1)O(2) production efficiency, based on the facet control of metal nanocrystals. In the cases of both organic oxidation and cancer treatment, it has been exclusively proven that the efficiency of producing singlet O(2) holds the key to the performance of Pd nanocrystals in the applications.

The currently low delivery efficiency and limited tumor penetration of nanoparticles remain two major challenges of cancer nanomedicine. Here, we report a class of pH-responsive nanoparticle superstructures with ultrasensitive size switching in the acidic tumor microenvironment for improved tumor penetration and effective in vivo drug delivery. The superstructures were constructed from amphiphilic polymer directed assembly of platinum-prodrug conjugated polyamidoamine (PAMAM) dendrimers, in which the amphiphilic polymer contains ionizable tertiary amine groups for rapid pH-responsiveness. These superstructures had an initial size of ∼80 nm at neutral pH (e.g., in blood circulation), but once deposited in the slightly acidic tumor microenvironment (pH ∼6.5-7.0), they underwent a dramatic and sharp size transition within a very narrow range of acidity (less than 0.1-0.2 pH units) and dissociated instantaneously into the dendrimer building blocks (less than 10 nm in diameter). This rapid size-switching feature not only can facilitate nanoparticle extravasation and accumulation via the enhanced permeability and retention effect but also allows faster nanoparticle diffusion and more efficient tumor penetration. We have further carried out comparative studies of pH-sensitive and insensitive nanostructures with similar size, surface charge, and chemical composition in both multicellular spheroids and poorly permeable BxPC-3 pancreatic tumor models, whose results demonstrate that the pH-triggered size switching is a viable strategy for improving drug penetration and therapeutic efficacy.

Aggregation and dissolution of poly(N-isopropylacrylamide) (PNIPAM) in water were investigated using an ultrasensitive differential scanning calorimetry (US-DSC) and a pressure perturbation calorimetry (PPC). US-DSC reveals that both the aggregation and dissolution of PNIPAM chains are greatly dependent on the scanning rate, indicating that the processes are kinetically controlled. The hysteresis in the dissolution process was found to have a nonequilibrium nature, which is thought to be related to the additional hydrogen bondings formed in the collapsed state of PNIPAM chains. A bimodal appearing in the cooling process at a slow scanning rate indicates the dissolution involves two different processes, i.e., the disruption of additional hydrogen bondings and the dissolution of the collapsed chains. PPC reveals that the solvent accessible surface area of PNIPAM chains in the cooling process is smaller than that in the heating process, which further indicates the dissolution of the PNIPAM aggregates involves such two processes.