A log symplectic manifold is a Poisson manifold which is generically nondegenerate. We develop two methods for constructing the symplectic groupoids of log symplectic manifolds. The first is a blow-up construction, corresponding to the notion of an elementary modification of a Lie algebroid along a subalgebroid. The second is a gluing construction, whereby groupoids defined on the open sets of an appropriate cover may be combined to obtain global integrations. This allows us to classify all Hausdorff symplectic groupoids of log symplectic manifolds in a combinatorial fashion, in terms of a certain graph of fundamental groups associated to the manifold. Using the same ideas, and as a first step, we also construct and classify the groupoids integrating the Lie algebroid of vector fields tangent to a smooth hypersurface.

Chemotherapeutic nanomedicines can exploit the neighboring effect to increase tumor penetration. However, the neighboring effect is limited, likely by the consumption of chemotherapeutic agents and resistance of internal hypoxic tumor cells. Here, we first propose and demonstrate that apoptotic bodies (ApoBDs) could carry the remaining drugs to neighboring tumor cells after apoptosis. To enhance the ApoBD-based neighboring effect, we fabricated disulfide-linked prodrug nanoparticles consisting of camptothecin (CPT) and hypoxia-activated prodrug PR104A. CPT kills external normoxic tumor cells to produce ApoBDs, while PR104A remains inactive. The remaining drugs could be effectively delivered into internal tumor cells via ApoBDs. Although CPT exhibits low toxicity to internal hypoxic tumor cells, PR104A could be activated to exert strong cytotoxicity, which further facilitates deep penetration of the remaining drugs. Such a synergic approach could overcome the limitations of the neighboring effect to penetrate deep into solid tumors for whole tumor destruction.

Prodrug-nanoparticles turn the disadvantage of the aggregation-caused quenching effect into an advantage to promote dual-modality PR104A release. Besides, photodynamic therapy-induced hypoxia activates PR104A for high-efficiency synergistic therapy.

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