Multivalent Binding and Biomimetic Cell Rolling Improves the Sensitivity and Specificity of Circulating Tumor Cell Capture.

We aimed to examine the effects of multivalent binding and biomimetic cell rolling on the sensitivity and specificity of circulating tumor cell (CTC) capture. We also investigated the clinical significance of CTCs and their kinetic profiles in patients with cancer undergoing radiotherapy treatment. Patients with histologically confirmed primary carcinoma undergoing radiotherapy, with or without chemotherapy, were eligible for enrollment.

Integration of biomimicry and nanotechnology for significantly improved detection of circulating tumor cells (CTCs).

Circulating tumor cells (CTCs) have received a great deal of scientific and clinical attention as a biomarker for diagnosis and prognosis of many types of cancer. Given their potential significance in clinics, a variety of detection methods, utilizing the recent advances in nanotechnology and microfluidics, have been introduced in an effort of achieving clinically significant detection of CTCs. However, effective detection and isolation of CTCs still remain a tremendous challenge due to their extreme rarity and phenotypic heterogeneity.

Intermolecular Structural Change for Thermoswitchable Polymeric Photosensitizer.

We developed a thermoswitchable polymeric photosensitizer (T-PPS) by conjugating PS (Pheophorbide-a, PPb-a) to a temperature-responsive polymer backbone of biocompatible hydroxypropyl cellulose. Self-quenched PS molecules linked in close proximity by π-π stacking in T-PPS were easily transited to an active monomeric state by the temperature-induced phase transition of polymer backbones. The temperature-responsive intermolecular interaction changes of PS molecules in T-PPS were demonstrated in synchrotron small-angle X-ray scattering and UV-vis spectrophotometer analysis.

Acidic pH-Triggered Drug-Eluting Nanocomposites for Magnetic Resonance Imaging-Monitored Intra-arterial Drug Delivery to Hepatocellular Carcinoma.

Transcatheter hepatic intra-arterial (IA) injection has been considered as an effective targeted delivery technique for hepatocellular carcinoma (HCC). Recently, drug-eluting beads (DEB) were developed for transcatheter IA delivery to HCC. However, the conventional DEB has offered relatively modest survival benefits.

Photosensitizer-Conjugated Hyaluronic Acid-Shielded Polydopamine Nanoparticles for Targeted Photomediated Tumor Therapy.

Photodynamic therapy (PDT) is a widely used clinical option for tumor therapy. However, the clinical utilization of conventional small-molecule photosensitizers (PSs) for PDT has been limited by their low selectivity for disease sites, and undesirable photoactivation. To overcome these limitations, we demonstrated a tumor-specific and photoactivity-controllable nanoparticle photomedicine based on a combination of PS-biomacromolecule conjugates and polydopamine nanoparticles (PD-NP) for an effective tumor therapy.

Reactive oxygen species responsive drug releasing nanoparticle based on chondroitin sulfate-anthocyanin nanocomplex for efficient tumor therapy.

To develop a reactive oxygen species (ROS) sensitive drug carrier, a chondroitin sulfate (CS)-anthocyanin (ATC) based nanocomplex was developed. Doxorubicin hydrochloride (DOX) was loaded in the CS-ATC nanocomplex (CS-ATC-DOX) via intermolecular stacking interaction. The nanocomplex was fabricated by a simple mixing method in the aqueous phase.

Recent advances in nanotechnology-based detection and separation of circulating tumor cells.

Although circulating tumor cells (CTCs) in blood have been widely investigated as a potential biomarker for diagnosis and prognosis of metastatic cancer, their inherent rarity and heterogeneity bring tremendous challenges to develop a CTC detection method with clinically significant specificity and sensitivity. With advances in nanotechnology, a series of new methods that are highly promising have emerged to enable or enhance detection and separation of CTCs from blood. In this review, we systematically categorize nanomaterials, such as gold nanoparticles, magnetic nanoparticles, quantum dots, graphenes/graphene oxides, and dendrimers and stimuli-responsive polymers, used in the newly developed CTC detection methods.

Vitamin Bc -Bearing Hydrophilic Photosensitizer Conjugate for Photodynamic Cancer Theranostics.

The accurate diagnosis and proper therapy for cancer are essential to improve the success rate of cancer treatment. Here, we demonstrated that the vitamin Bc -bearing hydrophilic photosensitizer conjugate folic acid-polyethylene glycol-pheophorbideA (FA-PEG-PheoA) has been synthesized for the intracellular diagnosis and photodynamic therapy of a tumor. The synthesized vitamin Bc -bearing hydrophilic photosensitizer conjugate has been characterized for the folic acid receptor expressing the ability to target tumor cells, which is facilitated by the chemical conjugation with folic acid.

Multifunctional tumor pH-sensitive self-assembled nanoparticles for bimodal imaging and treatment of resistant heterogeneous tumors.

Nanoparticle-based diagnosis-therapy integrative systems represent an emerging approach to cancer treatment. However, the diagnostic sensitivity, treatment efficacy, and bioavailability of nanoparticles as well as the heterogeneity and drug resistance of tumors pose tremendous challenges for clinical implementation. We herein report on the fabrication of tumor pH-sensitive magnetic nanogrenades (termed PMNs) composed of self-assembled iron oxide nanoparticles and pH-responsive ligands.

Endolysosomal environment-responsive photodynamic nanocarrier to enhance cytosolic drug delivery via photosensitizer-mediated membrane disruption.

The endolysosome is a major barrier for the effective intracellular delivery by conventional nanocarriers. Herein, we demonstrate that endolysosome environment-responsive photodynamic nanocarriers (EPNs) are capable of encapsulation of the hydrophobic drug paclitaxel (PTX) and photosensitizer (PS)-mediated ELB disruption for effective cancer therapy. EPNs were self-assembled from PS (chlorin e6, Ce6) or Black Hole Quencher-3 (BHQ3) conjugated covalently to polypeptide-based amphiphilic copolymers [monomethoxy polyethylene glycol-block-poly(β-benzyl-L-aspartic acid), mPEG-pBLA].

Photo-mediated internalization of nanocomplex for effective gene delivery to adipose tissue-derived stem cells.

To deliver efficiently osteogenic, chondrogenic or adipogenic induction genes, such as Runx2, SOX9 and C/EBP-α, to adipose tissue-derived stem cells (ADSCs), a photo-mediated nanocomplex internalization gene delivery system was designed using chlorin e6 as a photosensitizer (PS) and polyethyleneimine (PEI) as a gene delivery carrier. In this system, gene delivery efficacy was significantly increased in ADSCs by photo irradiation. The gene transfection efficiency of Runx2, SOX9 and C/EBP-α was increased by 8.

Photo-activatable ternary complex based on a multifunctional shielding material for targeted shRNA delivery in cancer treatment.

A photo-activatable ternary complex (PTC) consisting of multifunctional shielding material (MSM) with photosensitizer (PS)-conjugated chondroitin sulfate and polyethyleneimine based binary complexes containing epidermal growth factor receptor (EGFR)-shRNA delivery for CD44 targeted cancer therapy has been developed. The PTC has a negative surface charge of -37.9 mV, and a size of approximately 90 nm, and the ternary complexes were found to be stable against plasma proteins.

Biodegradable cationic nanoparticles loaded with an anticancer drug for deep penetration of heterogeneous tumours.

To enhance limited drug penetration that mediated drug resistance and heterogeneity within the tumour microenvironment, we designed a paclitaxel (PTX) loaded degradable cationic nanogel (DpNG) consisted with acetylated pullulan and low molecular weight polyethyleneimine ((Low)bPEI, 1.8 kDa). The restoration of cationic charge on the DpNG was achieved via HA degradation by hyaluronidase which is secreted in tumour.

Hyaluronic acid-conjugated graphene oxide/photosensitizer nanohybrids for cancer targeted photodynamic therapy.

Hyaluronic acid (HA)-graphene oxide (GO) conjugates, with a high loading of photosensitizers (PS; Ce6), were developed as a cancer cell targeted and photoactivity switchable nanoplatform for photodynamic therapy (PDT). HA-GO conjugates with size below 100 nm were first prepared by the chemical conjugation between ADH-modified HA and fractionated GO sheets with size relevant for drug delivery. Before evaluating the drug delivery efficacies, their chemical structure, morphology, and biocompatibility were characterized by H NMR, UV, TGA, AFM, DLS and MTT assays.

The transfection efficiency of photosensitizer-induced gene delivery to human MSCs and internalization rates of EGFP and Runx2 genes.

To improve the transfection efficiency of non-viral gene vectors to human mesenchymal stem cells (hMSCs), a photosensitizer (PS)-induced gene delivery system was designed by using pheophorbide-a (pheo-a) as a PS. In FACS results, this system showed excellent gene transfection efficiency depending on irradiation power. The result was strongly supported by western blot and real-time quantitative PCR (RT-qPCR) assays.

The controlled photoactivity of nanoparticles derived from ionic interactions between a water soluble polymeric photosensitizer and polysaccharide quencher.

In order to design a water soluble polymeric photosensitizer (WPS) with controllable photoactivity, a nano-photosensitizer (NPS) was prepared from a polyelectrolyte complex between polyethylene glycol-polyethylenimine-chlorine e6 conjugate (PEG-PEI-Ce6) and Black Hole Quencher-3 chondroitin sulfate conjugate (BHQ-3-CS). NPSs have a unimodal size distribution below 100 nm. Photoquenching of the NPS was dependent on the weight ratio of BHQ-3-CS/WPS.

Potential of self-organizing nanogel with acetylated chondroitin sulfate as an anti-cancer drug carrier.

In order to obtain feasibility data regarding the possibility of using chondroitin sulfate (CS) in an anti-cancer drug delivery system, CS was chemically modified by a one-step process with acetic anhydride. Although 3 samples with different degrees of acetylation were synthesized, only the sample with the highest degree of acetylation (AC-CS3) was tested as a nanogel because the others (AC-CS1 and 2) dissolved in distilled water (DW) in the test range (1-10 mg/ml). The AC-CS3 nanogel was characterized by fluorescence probe and dynamic light scattering (DLS) techniques.