The ability to efficiently deliver a drug to a tumor site is dependent on a wide range of physiologically imposed design constraints. Nanotechnology provides the possibility of creating delivery vehicles where these design constraints can be decoupled, allowing new approaches for reducing the unwanted side effects of systemic delivery, increasing targeting efficiency and efficacy. Here we review the design strategies of the two FDA-approved antibody-drug conjugates (Brentuximab vedotin and Trastuzumab emtansine) and the four FDA-approved nanoparticle-based drug delivery platforms (Doxil, DaunoXome, Marqibo, and Abraxane) in the context of the challenges associated with systemic targeted delivery of a drug to a solid tumor. The lessons learned from these nanomedicines provide important insight into the key challenges associated with the development of new platforms for systemic delivery of anti-cancer drugs.
The water solubilization of nanoparticles is key for many applications in biomedicine. Despite the importance of surface functionalization, progress has been largely empirical and very few systematic studies have been performed. Here we report on the water solubilization of QDs using lipid encapsulation. We systematically evaluate the monodispersity, zeta potential, stability, and quantum yield (QY) for QDs encapsulated with single and double acyl chain lipids, pegylated double acyl chain lipids, and single alkyl chain surfactant molecules with charged head groups. We show that charged surfactants and pegylated lipids are important to obtain monodisperse suspensions with high yield and excellent long-term stability.
Recent studies have found that prostate cancer expresses abnormal genetic markers including multiple types of
TMPRSS2–ERG
fusion genes. The expression level of different
TMPRSS2–ERG
fusion genes is correlated to pathologic variables of aggressive prostate cancer and disease progression. State-of-the-art methods for detection of
TMPRSS2–ERG
fusion genes include reverse transcription polymerase chain reaction (RT-PCR) with a detection limit of 1 fmol at urinary condition. RT-PCR is time consuming, costly, and inapplicable for multiplexing. Ability to identify multiple fusion genes in a single sample has become important for diagnostic and clinical purposes. There is a need for a sensitive diagnostic test to detect multiple
TMPRSS2–ERG
fusion genes for an early diagnosis and prognosis of prostate cancer. Here, we propose to develop an assay for prostate cancer diagnosis using oligonucleotide-functionalized quantum dot and magnetic microparticle for optical detection of rearranged
TMPRSS2–ERG
fusion genes at a low concentration in urine. We found that our assay was able to identify three different types of fusion gene with a wide detection range and detection limit of 1 fmol (almost the same level of the RT-PCR result reported). Here, we show detection of multiple
TMPRSS2–ERG
fusion genes using color-coded oligonucleotides in cell lysate and urine.
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