Ashwinkumar Bhirde

Photosensitizer Loaded Nano-Graphene for Multimodality Imaging Guided Tumor Photodynamic Therapy

Graphene, a 2-dimensional carbon nanomaterial, has attracted wide attention in biomedical applications, owing to its intrinsic physical and chemical properties. In this work, a photosensitizer molecule, 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-alpha (HPPH or Photochlor®), is loaded onto polyethylene glycol (PEG)-functionalized graphene oxide (GO) via supramolecular π-π stacking. The obtained GO-PEG-HPPH complex shows high HPPH loading efficiency. The in vivo distribution and delivery were tracked by fluorescence imaging as well as positron emission tomography (PET) after radiolabeling of HPPH with 64Cu. Compared with free HPPH, GO-PEG-HPPH offers dramatically improved photodynamic cancer cell killing efficacy due to the increased tumor delivery of HPPH. Our study identifies a role for graphene as a carrier of PDT agents to improve PDT efficacy and increase long-term survival following treatment.

A nanoscale graphene oxide-peptide biosensor for real-time specific biomarker detection on the cell surface.

A nanoscale RGD-pyrene-graphene oxide (GO) biosensor was prepared for real-time in situ detection of a cancer cell surface marker, integrin αvβ3. This nanoscale GO-based biosensor is simple, robust, sensitive and of high selectivity. It can also be adapted to other cancer cell surface marker evaluation systems.

Hollow iron oxide nanoparticles as multidrug resistant drug delivery and imaging vehicles

AbstractMagnetic nanoparticles have been used as drug delivery vehicles against a number of cancer cells. Most of these theranostic formulations have used solid iron oxide nanoparticles (SIONPs) loaded with chemotherapeutics as nano-carrier formulation for both magnetic resonance imaging (MRI) and cancer therapy. In this study, we applied the dopamine-plus-human serum albumin (HSA) method to modify hollow iron oxide nanoparticles (HIONPs) and encapsuated doxorubicin (DOX) within the hollow porous structure of the nano-carrier. The new delivery system can load more drug than solid iron oxide nanoparticles of the same core size using the same coating strategy. The HIONPs-DOX formulation also has a pH-dependent drug release behaviour. Compared with free DOX, the HIONPs-DOX were more effectively uptaken by the multidrug resistant OVCAR8-ADR cells and consequently more potent in killing drug resistant cancer cells. MRI phantom and cell studies also showed that the HIONPs-DOX can decrease the T2 MRI signal intensity and can be used as a MRI contrast agent while acting as a drug delivery vehicle. For the first time, the dual application of chemo drug transport and MR imaging using the HIONPs-DOX formulation was achieved against both DOX-sensitive and DOX-resistant cancer cells.

A facile, one-step nanocarbon functionalization for biomedical applications

Despite their immense potential in biomedicine, carbon nanomaterials suffer from inefficient dispersion and biological activity in vivo. Here we utilize a single, yet multifunctional, hyaluronic acid-based biosurfactant to simultaneously disperse nanocarbons and target single-walled carbon nanotubes (SWCNTs) to CD44 receptor positive tumor cells with prompt uptake. Cellular uptake was monitored by intracellular enzyme-activated fluorescence, and localization of SWCNTs within cells was further confirmed by Raman mapping. In vivo photoacoustic, fluorescence, and positron emission tomography imaging of coated SWCNTs display high tumor targeting capability while providing long-term, fluorescence molecular imaging of targeted enzyme events. By utilizing a single biomaterial surfactant for SWCNT dispersion without additional bioconjugation, we designed a facile technique that brings nanocarbons closer to their biomedical potential.

Highly Robust, Recyclable Displacement Assay for Mercuric Ions in Aqueous Solutions and Living Cells

We designed a recyclable Hg(2+) probe based on Rhodamine B isothiocyanate (RBITC)-poly(ethylene glycol) (PEG)-comodified gold nanoparticles (AuNPs) with excellent robustness, selectivity, and sensitivity. On the basis of a rational design, only Hg(2+) can displace RBITC from the AuNP surfaces, resulting in a remarkable enhancement of RBITC fluorescence initially quenched by AuNPs. To maintain stability and monodispersity of AuNPs in real samples, thiol-terminated PEG was employed to bind with the remaining active sites of AuNPs. Besides, this displacement assay can be regenerated by resupplying free RBITC into the AuNPs solutions that were already used for detecting Hg(2+). Importantly, the detection limit of this assay for Hg(2+) (2.3 nM) was lower than the maximum limits guided by the United States Environmental Protection Agency as well as that permitted by the World Health Organization. The efficiency of this probe was demonstrated in monitoring Hg(2+) in complex samples such as river water and living cells.

Sticky Nanoparticles: A Platform for siRNA Delivery by a Bis(zinc(II) dipicolylamine)‐Functionalized, Self‐Assembled Nanoconjugate

Delivering the goods: Multifunctional, self-assembled, polymeric nanoparticles for the simultaneous delivery of small-molecule drugs and siRNA have been synthesized. The nanoparticles are composed of biodegradable hyaluronic acid, for tumor targeting and cellular delivery, and a high siRNA binding affinity is provided by a Zn(II)-dipicolylamine analogue as an artificial phosphate-binding receptor (see scheme).

Multiplex Imaging of an Intracellular Proteolytic Cascade by using a Broad-Spectrum Nanoquencher

Proteases are known as extremely important signaling molecules and the deregulation of specific protease activities can ultimately lead to severe pathologies, which include cardiovascular disease, osteoporosis, inflammatory disease, neurodegenerative disorders, and cancer.[1] Therefore, identifying the role of a specific protease in a given biological process is crucial to promote new approaches for the prevention of diseases.[2] A system that enables the direct and simultaneous monitoring of multiple proteolytic activities in living organisms has great potential for elucidating complex protease signaling pathways, as well as testing the efficacy of drugs that target proteases.

Targeted Therapeutic Nanotubes Influence the Viscoelasticity of Cancer Cells to Overcome Drug Resistance

Resistance to chemotherapy is the primary cause of treatment failure in over 90% of cancer patients in the clinic. Research in nanotechnology-based therapeutic alternatives has helped provide innovative and promising strategies to overcome multidrug resistance (MDR). By targeting CD44-overexpressing MDR cancer cells, we have developed in a single-step a self-assembled, self-targetable, therapeutic semiconducting single-walled carbon nanotube (sSWCNT) drug delivery system that can deliver chemotherapeutic agents to both drug-sensitive OVCAR8 and resistant OVCAR8/ADR cancer cells. The novel nanoformula with a cholanic acid-derivatized hyaluronic acid (CAHA) biopolymer wrapped around a sSWCNT and loaded with doxorubicin (DOX), CAHA-sSWCNT-DOX, is much more effective in killing drug-resistant cancer cells compared to the free DOX and phospholipid PEG (PL-PEG)-modified sSWCNT formula, PEG-sSWCNT-DOX. The CAHA-sSWCNT-DOX affects the viscoelastic property more than free DOX and PL-PEG-sSWCNT-DOX, which in turn allows more drug molecules to be internalized. Intravenous injection of CAHA-sSWCNT-DOX (12 mg/kg DOX equivalent) followed by 808 nm laser irradiation (1 W/cm2, 90 s) led to complete tumor eradication in a subcutaneous OVCAR8/ADR drug-resistant xenograft model, while free DOX alone failed to delay tumor growth. Our newly developed CAHA-sSWCNT-DOX nanoformula, which delivers therapeutics and acts as a sensitizer to influence drug uptake and induce apoptosis with minimal resistance factor, provides a novel effective means of counteracting the phenomenon of multidrug resistance.

Carbon-dot-based two-photon visible nanocarriers for safe and highly efficient delivery of siRNA and DNA.

A simple and versatile nanoparticulate siRNA and DNA delivery vehicle is reported, based on photonic Cdots by using Alkyl-PEI2k for surface passivation.

Functional MnO nanoclusters for efficient siRNA delivery

A non-viral gene delivery nanovehicle based on Alkyl-PEI2k capped MnO nanoclusters was synthesized via a simple, facile method and used for efficient siRNA delivery and magnetic resonance imaging.