Strategic Timing of Gene Silencing: Cellular Kinetics-Based Administration of siRNA for Optimized Photothermal Cancer Treatment.

Heat shock protein 70 (HSP70) represents a critical barrier to effective mild-temperature photothermal therapy (MPTT), limiting its clinical utility in aggressive cancers like triple-negative breast cancer (TNBC). While small interfering RNA (siRNA)-mediated HSP70 suppression offers a promising solution, optimal timing for this therapeutic combination remains unexplored. Here, it is demonstrated that precisely timed administration significantly enhances MPTT efficacy through systematic temporal characterization of HSP70 expression dynamics.

AMP coated SERS NanoTags with hydrophobic locking: Maximizing brightness, stability, and cellular targetability.

Developing innovative surface-enhanced Raman scattering (SERS) nanotags continues to attract significant attention due to their unparalleled sensitivity and specificity for in vitro diagnostic and in vivo tumor imaging applications. Here, we report a new class of bright and stable SERS nanotags using alkylmercaptan-PEG (AMP) polymers. Due to its amphiphilic structure and a thiol anchoring group, these polymers strongly absorb onto gold nanoparticles, leading to an inner hydrophobic layer and an outer hydrophilic PEG layer.

Alternating stealth polymer coatings between administrations minimizes toxic and antibody immune responses towards nanomedicine treatment regimens.

In efforts to achieve minimal systemic toxicity and high tumor delivery efficiencies in cancer therapy, various nanomedicine formulations having stealth polymer coatings have been developed for minimizing immune cell uptake and off-target macrophage phagocyte system (MPS) organ accumulation. Despite an initial reduction in immune cell uptake, stealth nanoparticles still initiate an antibody immune response. This response acts on subsequent administrations in treatment regimens resulting in accelerated blood clearance of particles into MPS organs, particularly the liver, where they are retained for prolonged periods.

Probing the biological obstacles of nanomedicine with gold nanoparticles.

Despite massive growth in nanomedicine research to date, the field still lacks fundamental understanding of how certain physical and chemical features of a nanoparticle affect its ability to overcome biological obstacles in vivo and reach its intended target. To gain fundamental understanding of how physical and chemical parameters affect the biological outcomes of administered nanoparticles, model systems that can systematically manipulate a single parameter with minimal influence on others are needed. Gold nanoparticles are particularly good model systems in this case as one can synthetically control the physical dimensions and surface chemistry of the particles independently and with great precision.

Method for Real-Time Tissue Quantification of Indocyanine Green Revealing Optimal Conditions for Near Infrared Fluorescence Guided Surgery.

Near infrared fluorescence guided surgery (NIRFGS) offers better distinction between cancerous and normal tissues compared to surgeries relying on a surgeon's senses of sight and touch. Because of the greater accuracy in determining tumor tissue margins, NIRFGS within clinics continues to grow. However, NIRFGS lacks standardization of the indocyanine green (ICG) dose and the preoperative period allowed after ICG administration.

Emergence of two near-infrared windows for in vivo and intraoperative SERS.

Two clear windows in the near-infrared (NIR) spectrum are of considerable current interest for in vivo molecular imaging and spectroscopic detection. The main rationale is that near-infrared light can penetrate biological tissues such as skin and blood more efficiently than visible light because these tissues scatter and absorb less light at longer wavelengths. The first clear window, defined as light wavelengths between 650nm and 950nm, has been shown to be far superior for in vivo and intraoperative optical imaging than visible light.

Quantitative Examination of the Active Targeting Effect: The Key Factor for Maximal Tumor Accumulation and Retention of Short-Circulated Biopolymeric Nanocarriers.

Targeted and nontargeted biopolymeric nanoparticles with identical hydrodynamic sizes and surface charges were quantitatively examined in terms of the pharmacokinetic and biodistribution differences in detail. In adding cancer cell targeting folate molecules to the surface of the heparin nanocarriers, the amount of drug delivered to the tumor is doubled, and tumor growth inhibition is significantly enhanced. The folate-targeted heparin particles offered similar therapeutic potentials compared to their synthetic long-circulating analogues, thus presenting a viable alternative for drug-delivery vehicle construction using biological polymers, which are easier for the body to eliminate.

Functionalized, Long-Circulating, and Ultrasmall Gold Nanocarriers for Overcoming the Barriers of Low Nanoparticle Delivery Efficiency and Poor Tumor Penetration.

The development of sophisticated nanoplatforms for in vivo targeted delivery of therapeutic agents to solid tumors has the potential for not only improving therapeutic efficacy but also minimizing systemic toxicity. However, the currently low delivery efficiency (about 1% of the injected dose) and the limited tumor penetration of nanoparticles remain two major challenges. Here we report a class of functionalized, long-circulating, and ultrasmall gold nanocarriers (5 nm gold core and 20 nm overall hydrodynamic diameter) for improved drug delivery and deep tumor penetration.

Enhanced Detection Specificity and Sensitivity of Alzheimer's Disease Using Amyloid-β-Targeted Quantum Dots.

Diagnostics of Alzheimer's disease (AD) commonly employ the use of fluorescent thioflavin derivatives having affinity for the amyloid-β (Aβ) proteins associated with AD progression. However, thioflavin probes have limitations in their diagnostic capabilities arising from a number of undesireable qualities, including poor photostability, weak emission intensity, and high emission overlap with the backgound tissue autofluorescence. To overcome such limitations, we have developed nanoformulated probes consisting of a red-emitting fluorescent quantum dot (QD) core encapsulated in a PEGylated shell with benzotriazole (BTA) targeting molecules on the surface (QD-PEG-BTA).

Stimuli-responsive nanoparticles for targeting the tumor microenvironment.

One of the most challenging and clinically important goals in nanomedicine is to deliver imaging and therapeutic agents to solid tumors. Here we discuss the recent design and development of stimuli-responsive smart nanoparticles for targeting the common attributes of solid tumors such as their acidic and hypoxic microenvironments. This class of stimuli-responsive nanoparticles is inactive during blood circulation and under normal physiological conditions, but is activated by acidic pH, enzymatic up-regulation, or hypoxia once they extravasate into the tumor microenvironment.

An unusual role of folate in the self-assembly of heparin-folate conjugates into nanoparticles.

Tumor targeting agents including antibodies, peptides, and small molecules, are often used to improve the delivery efficiency of nanoparticles. Despite numerous studies investigating the abilities of targeting agents to increase the accumulation of nanosized therapeutics within diseased tissues, little attention has been focused on how these ligands can affect the self-assembly of the nanoparticle's modified polymer constituents upon chemical conjugation. Here we present an actively tumor targeted nanoparticle constructed via the self-assembly of a folate modified heparin.

Physical chemistry of nanomedicine: understanding the complex behaviors of nanoparticles in vivo.

Nanomedicine is an interdisciplinary field of research at the interface of science, engineering, and medicine, with broad clinical applications ranging from molecular imaging to medical diagnostics, targeted therapy, and image-guided surgery. Despite major advances during the past 20 years, there are still major fundamental and technical barriers that need to be understood and overcome. In particular, the complex behaviors of nanoparticles under physiological conditions are poorly understood, and detailed kinetic and thermodynamic principles are still not available to guide the rational design and development of nanoparticle agents.

Compact and blinking-suppressed quantum dots for single-particle tracking in live cells.

Quantum dots (QDs) offer distinct advantages over organic dyes and fluorescent proteins for biological imaging applications because of their brightness, photostability, and tunability. However, a major limitation is that single QDs emit fluorescent light in an intermittent on-and-off fashion called "blinking". Here we report the development of blinking-suppressed, relatively compact QDs that are able to maintain their favorable optical properties in aqueous solution.

Mapping the spatial distribution of charge carriers in quantum-confined heterostructures.

Quantum-confined nanostructures are considered 'artificial atoms' because the wavefunctions of their charge carriers resemble those of atomic orbitals. For multiple-domain heterostructures, however, carrier wavefunctions are more complex and still not well understood. We have prepared a unique series of cation-exchanged Hg(x)Cd(1-x)Te quantum dots (QDs) and seven epitaxial core-shell QDs and measured their first and second exciton peak oscillator strengths as a function of size and chemical composition.