Wavefront propagation based on the ray transfer matrix and numerical orthogonal Zernike gradient polynomials.

The aberrated wavefront propagates along its normal. Both the magnitude and boundary change after the propagation. Wavefronts characterized by Zernike coefficients and a normalized pupil radius can also be represented by a bundle of feature rays normal to the local surface. A ray transfer matrix parameterized by the pupil radius and propagation distance is proposed to transfer these feature rays to obtain the slope and position data of the propagated feature rays. Numerical orthogonal Zernike gradient polynomials are derived to reconstruct the wavefront from the discrete data by using a numerical method. Two aberrated wavefronts are performed as examples to validate the accuracy and flexibility of the proposed numerical method.

Transforming a highly toxic agent DM1 into injectable safe nanomedicines via prodrug self-assembly for the treatment of taxane-resistant cancer.

Drug resistance is one of the major obstacles for successful chemotherapy of malignant tumors including cervical cancer. To overcome this problem, a lot of efforts have been made, and drug nanoformulation may be a possible solution. Maytansine and its derivatives, the powerful tubulin polymerization inhibitors, have superior anti-tumor activity toward multiple malignant tumors compared with most anti-tumor drugs including doxorubicin, camptothecin, and cabazitaxel in current clinical studies. Nevertheless, they are hard to be accepted as clinical drugs due to their systemic toxicity to the human body, no tumor targeting, and insolubility in aqueous solutions. In this work, a strategy, called PUFAylation, has been developed to modify maytansinoid (DM1) with a polyunsaturated fatty acid (PUFA) to solve these problems by covalently coupling DM1 and docosahexaenoic acid (DHA). Two types of PUFAylated prodrugs (i.e., dSS-DM1 and dMT-DM1), prepared through different linking strategies via a thiol-disulfide exchange reaction and maleimide-thiol reaction, respectively, can self-assemble in aqueous solution to form nanoassemblies (NAs) for preclinical study by intravenous injection. In a BALB/c nude mouse model bearing cell-derived xenografts, there was no significant weight loss in mouse groups treated with dSS-DM1 NAs and dMT-DM1 NAs. In contrast, the mice with intravenous injection of free DM1 suffered a significant weight loss during the treatment. At the same time, dMT-DM1 NAs exhibit similar anti-tumor effects to free DM1 (p > 0.05). Overall, by modification of the chemotherapeutic drugs, the systemic toxicity and side effects of DM1 can be effectively reduced without sacrificing its anti-tumor effect. Particularly, dMT-DM1 NAs had shown superior therapeutic effects against drug-resistant cervical cancer and may be a potential alternative for clinical treatment of cervical cancer with paclitaxel resistance. Furthermore, this DM1-formulated platform may be applied to other anticancer agents due to its simplicity.

Microfluidic assembly of small-molecule prodrug cocktail nanoparticles with high reproducibility for synergistic combination of cancer therapy.

Therapeutic nanoparticles (NPs) self-assembled from small molecular (pro)drug entities, opens up novel avenues for the generation of a wide range of drug delivery systems. Particularly, cocktail NPs created by co-assembly of multiple therapeutics often show profound efficacy beyond their individual agents. However, fabrication of synergistic NPs with high reproducibility and capability to deliver multiple therapeutics in a predefined ratio remains a challenge, which deters NP therapeutics from further clinical translation. In this work, a simple but versatile strategy has been developed to combine drug reconstitution and supramolecular nanoassembly to prodrug cocktail nanoparticle fabrication with microfluidics. Prodrugs reconstructed by PUFAylation were self-assembled into hybrid nanoparticles via microfluidic chip to synergistically deliver two chemotherapeutic drugs, 7-ethyl-10-hydroxy camptothecin (SN38) and paclitaxel (PTX), in a single nanoparticle container. In vitro cell-based assays demonstrate that the combinatorial chemotherapy is superior to each prodrug used alone while reduces the dosage of both drugs at the same time. Furthermore, the double-drug combination suppresses colon tumors by 86% at a total dosage of 16.7 mg/kg through synergy, and histological analysis indicates the safety of the hybrid nanoparticles. In general, this work shows that the nanomedicine synthesized by microfluidics provides considerable advantages including better size control and reproducibility, and great potential in effective combination therapy. It is expected to be applied to the fabrication of more chemical agent combination for other cancer types.