In this work, we report the synthesis of novel fluorescent molecules, based on 1,8-naphthalimide thio- and amino-derivatives, designed to display an OFF-ON and ON-OFF photoelectron transfer fluorescence switch upon interaction with a proton-donor drug. We have functionalized the new probes to allow easy formation of a covalent link to polymer matrices, for future applications as drug delivery sensors. We have investigated the fluorescent switch of the new probes using flufenamic acid (FA, pKa 3.65), a water insoluble, non-steroidal anti-inflammatory drug, as a model drug and proton source. The rapid interaction of the new probes with FA resulted in fluorescence enhancement or decrease and a large Stokes shift, all of which allowed the detection of the drug in the nanomolar range. The new 1,8-naphthalimide fluorescent dyes reported in this work are interesting tools for the detection and quantification of acidic drugs and biomolecules.

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide with poor prognosis and limited options for treatment. Life expectancy after diagnosis is short; the currently available treatments are not well tolerated and have limited clinical benefit. There is a clear unmet clinical need for the development of new treatments. In this study, ultrasmall, 2 nm gold core nanoparticles (MidaCore) conjugated with the potent maytansine analogue DM1 (MTC-100038) were assessed as a systemic nanomedicine for the treatment of hepatocellular carcinoma. The platform improved overall tolerability of DM1, permitting ∼3fold higher levels of drug to be administered compared to free drug. Dose for dose, MTC-100038 also facilitated delivery of ∼2.0-fold higher (p = 0.039) levels of DM1 to the tumor compared to free DM1. MTC-100038 produced significant efficacy (tumor growth index ∼102%; p = <0.0001), in several murine xenograft models of HCC, and was superior to both free DM1 and the current standard of care, sorafenib. Furthermore, MTC-100038 displayed potent (nM) in vitro activity in various HCC primary patient derived cell lines and across various other different cancer cell types. These data demonstrate the potential of MidaCore nanoparticles to enhance tumor delivery of cytotoxic drugs and indicate MTC-100038 is worthy of further investigation as a potential treatment for HCC and other cancer types.

Several fluorescent molecularly imprinted nanogels for the detection of the anticancer drug sunitinib were synthesized and characterized. A selection of functional monomers based on different aminoacids and coumarin allowed isolation of polymers with very good rebinding properties and sensitivities. The direct detection of sunitinib in human plasma was successfully demonstrated by fluorescence quenching of the coumarin-based nanogels. The plasma sample simply diluted in DMSO allowed the recovery of various amounts of sunitib, as determined by an averaged calibration curve. The LOD was 400nM, with within-run variability <9%, day to day variability <5%, and good accuracy in the recovery of sunitinib from spiked samples.

Genetically modified autologous T cells have become an established immunotherapy in the fight against cancer. The manufacture of chimeric antigen receptor (CAR) and αβ-T cell receptor (TCR) transduced T cells poses unique challenges, including the formulation, cryopreservation and fill–finish steps, which are the focus of this review. With an increasing number of marketing approvals for CAR-T cell therapies, comparison of their formulation design and presentation for administration can be made. These differences will be discussed alongside the emergence of automated formulation and fill-finish processes, the formulation design space, Monte Carlo simulation applied to risk analysis, primary container selection, freezing profiles and thaw and the use of dimethyl sulfoxide and alternative solvents/excipients as cryopreservation agents. The review will conclude with a discussion of the pharmaceutical solutions required to meet the simplification of manufacture and flexibility in dosage form for clinical treatment.

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