Advanced modification of drug nanocrystals by using novel fabrication and downstream approaches for tailor-made drug delivery

Drug nanosuspensions/nanocrystals have been recognized as one useful and successful approach for drug delivery. Drug nanocrystals could be further decorated to possess extended functions (such as controlled release) and designed for special in vivo applications (such as drug tracking), which make best use of the advantages of drug nanocrystals. A lot of novel and advanced size reduction methods have been invented recently for special drug deliveries. In addition, some novel downstream processes have been combined with nanosuspensions, which have highly broadened its application areas (such as targeting) besides traditional routes. A large number of recent research publication regarding as nanocrystals focuses on above mentioned aspects, which have widely attracted attention. This review will focus on the recent development of nanocrystals and give an overview of regarding modification of nanocrystal by some new approaches for tailor-made drug delivery

New Strategies to Improve Therapeutic Vaccines

Vaccination represents a viable and attractive strategy for therapeutic treatment of cancers by the power of a patient’s own immune system. Major advances in cellular and molecular immunology have led to the approval of the first therapeutic cancer vaccine by FDA. However, the development of cancer vaccines remains infant. Maximizing the therapeutic efficacy while minimizing side effects of the therapeutic cancer vaccine remains key challenges to this field. In this review, we summarized the recently developed strategies to induce anti-tumor responses in vivo to improve the outcomes of cancer vaccines, with an emphasis on the guiding principles that are critical for rational design of effective and safe vaccines against cancers

Using the Unfolded State as the Reference State Improves the Performance of Statistical Potentials

AbstractDistance-dependent statistical potentials are an important class of energy functions extensively used in modeling protein structures and energetics. These potentials are obtained by statistically analyzing the proximity of atoms in all combinatorial amino-acid pairs in proteins with known structures. In model evaluation, the statistical potential is usually subtracted by the value of a reference state for better selectivity. An ideal reference state should include the general chemical properties of polypeptide chains so that only the unique factors stabilizing the native structures are retained after calibrating on reference state. However, reference states available as of this writing rarely model specific chemical constraints of peptide bonds and therefore poorly reflect the behavior of polypeptide chains. In this work, we proposed a statistical potential based on unfolded state ensemble (SPOUSE), where the reference state is summarized from the unfolded state ensembles of proteins produced according to the statistical coil model. Due to its better representation of the features of polypeptides, SPOUSE outperforms three of the most widely used distance-dependent potentials not only in native conformation identification, but also in the selection of close-to-native models and correlation coefficients between energy and model error. Furthermore, SPOUSE shows promising possibility of further improvement by integration with the orientation-dependent side-chain potentials

Guiding Principles in the Design of Molecular Bioconjugates for Vaccine Applications

Antigen- and adjuvant-based bioconjugates that can stimulate the immune system play an important role in vaccine applications. Bioconjugates have demonstrated unique physicochemical and biological properties, enabling vaccines to be delivered to key immune cells, to target specific intracellular pathways, or to mimic immunogenic properties of natural pathogens. In this Review we highlight recent advances in such molecular immunomodulators, with an emphasis on the structure–function relationships that provide the foundation for rational design of safe and effective vaccines and immunotherapies.United States. National Institutes of Health (AI095109)United States. National Institutes of Health (AI091693)United States. National Institutes of Health (AI104715)Ragon Institute of MGH, MIT and HarvardDana-Farber Cancer Institute. Bridge Projec