A lipo-polymeric hybrid nanosystem with metal enhanced fluorescence for targeted imaging of metastatic breast cancer.

Cancer metastasis plays a major role in failure of therapeutic avenues against cancer. Owing to metastasis, nearly 70-80% of stage IV breast cancer patients lose their lives. Nanodrug delivery systems are playing a critical role in the therapy of metastatic cancer in the recent times. This paper reports the enhanced permeation and retention (EPR) based targeting of metastatic breast cancer using a novel nano lipo-polymeric system (PIR-Au NPs). The PIR-Au NPs demonstrated an increase in fluorescence by virtue of surface coating with gold, owing to the metal enhanced fluorescence phenomenon as reported in our earlier reports. Enhanced fluorescence of PIR-Au NPs was observed in murine mammary carcinoma cell line (4T1), as compared to free IR780 or IR780 loaded nanosystems (P-IR NPs), when incubated for same time at same concentrations, indicating its potential application for imaging and an enhanced bioavailability of IR780. Significant cell death was noted with photothermal mediated cytotoxicity in-vitro against breast cancer cells (MCF-7 and 4T1). An enhanced fluorescence was observed in the zebra fish embryos incubated with PIR-Au NPs. The enhanced permeation and retention (EPR) effect was seen with PIR-Au NPs in-vivo. A strong fluorescent signal was recorded in mice injected with PIR-Au NPs. The tumor tissue collected after 72 h, clearly showed a greater fluorescence as compared to other groups, indicating the plasmon enhanced fluorescence. We also demonstrated the EPR-based targeting of the PIR-Au NPs in-vivo by means of photothermal heat. This lipo-polymeric hybrid nanosystem could therefore be successfully applied for image-guided, passive-targeting to achieve maximum therapeutic benefits.

Development of a Point-of-Care Cervico-Vaginal Sampling/Testing Device for the Colorimetric Detection of Cervical Cancer.

This paper reports the colorimetric analysis of cervical-cancer-affected clinical samples by the in situ formation of gold nanoparticles (AuNPs) formed with cervico-vaginal fluids collected from healthy and cancer-affected patients in a clinical setup, termed "C-ColAur". We evaluated the efficacy of the colorimetric technique against the clinical analysis (biopsy/Pap smear) and reported the sensitivity and specificity. We investigated if the aggregation coefficient and size of the nanoparticles responsible for the change in color of the AuNPs (formed with clinical samples) could also be used as a measure of detecting malignancy. We estimated the protein and lipid concentrations in the clinical samples and attempted to investigate if either of these components was solely responsible for the color change, enabling their colorimetric detection. We also propose a self-sampling device, CerviSelf, that could enable the rapid frequency of screening. We discuss two of the designs in detail and demonstrate the 3D-printed prototypes. These devices, in conjugation with the colorimetric technique C-ColAur, have the potential to be self-screening techniques, enabling women to undergo rapid and frequent screening in the comfort and privacy of their homes, allowing a chance at an early diagnosis and improved survival rates.

A plasmon-enhanced fluorescent gold coated novel lipo-polymeric hybrid nanosystem: synthesis, characterization and application for imaging and photothermal therapy of breast cancer.

This study reports a hybrid lipo-polymeric nanosystem (PDPC NPs) synthesized by a modified hydrogel-isolation technique. The ability of the nanosystem to encapsulate hydrophilic and hydrophobic molecules has been demonstrated, and their enhanced cellular uptake has been observed in vitro. The PDPC NPs, surface coated with gold by in situ reduction of chloroauric acid (PDPC-Au NPs), showed a photothermal transduction efficacy of ∼65%. The PDPC-Au NPs demonstrated an increase in intracellular ROS, triggered DNA damage and resulted in apoptotic cell death when tested against breast cancer cells (MCF-7). The disintegration of PDPC-Au NPs into smaller nanoparticles with near-infrared (NIR) laser irradiation was understood using transmission electron microscopy imaging. The lipo-polymeric hybrid nanosystem exhibited plasmon-enhanced fluorescence when loaded with IR780 (a NIR dye), followed by surface coating with gold (PDPC-IR-Au NPs). This paper is one of the first reports on the plasmon-enhanced fluorescence within a nanosystem by simple surface coating of Au, to the best of our knowledge. This plasmon-enhanced fluorescence was unique to the lipo-polymeric hybrid system, as the same was not observed with a liposomal nanosystem. The plasmon-enhanced fluorescence of PDPC-IR-Au NPs, when applied for imaging cancer cells and zebrafish embryos, showed a strong fluorescence signal at minimal concentrations of the dye. The PDPC-IR-Au NPs were also applied for photothermal therapy of breast cancer in vitro and in vivo, and the results depicted significant therapeutic benefits.

The role played by bacterial infections in the onset and metastasis of cancer.

Understanding various responses of cells towards change in their external environment, presence of other species and is important in identifying and correlating the mechanisms leading to malignant transformations and cancer development. Although uncovering and comprehending the association between bacteria and cancer is highly challenging, it promises excellent perspectives and approaches for successful cancer therapy. This review introduces various bacterial species, their virulence factors, and their role in cell transformations leading to cancer (particularly gastric, oral, colon, and breast cancer). Bacterial dysbiosis permutates host cells, causes inflammation, and results in tumorigenesis. This review explored bacterial-mediated host cell transformation causing chronic inflammation, immune receptor hyperactivation/absconding immune recognition, and genomic instability. Bacterial infections downregulate E-cadherin, leading to loosening of epithelial tight junction polarity and triggers metastasis. In addition to understanding the role of bacterial infections in cancer development, we have also reviewed the application of bacteria for cancer therapy. The emergence of bacteriotherapy combined with conventional therapies led to new and effective ways of overcoming challenges associated with available treatments. This review discusses the application of bacterial minicells, microswimmers, and outer cell membrane vesicles (OMV) for drug delivery applications.

Sand bath assisted green synthesis of carbon dots from citrus fruit peels for free radical scavenging and cell imaging.

A sand bath assisted strategy for the synthesis of fluorescent carbon dots (CDs) using citrus fruit peels as a renewable green resource is reported in this work. The CDs were synthesized without any alkaline or acidic environment. The synthesized CDs were characterized by various spectroscopic and microscopy techniques. The CDs exhibited excellent water solubility and superior optical properties like excitation dependent emission, and multicolor fluorescence. In addition, the CDs have exhibited remarkable free radical scavenging activity (EC50: 4.7382 µg ml-1).The CDs were highly biocompatible and showed lower toxicity. The CDs when modified with folic acid have shown a significant potential as biological labels for cellular imaging at multiple excitations. Synthesis of CDs from natural fruit peels as an excellent carbon source for versatile applications has been demonstrated.

Light-triggered selective ROS-dependent autophagy by bioactive nanoliposomes for efficient cancer theranostics.

Light-responsive nanoliposomes are being reported to induce cancer cell death through heat and reactive oxygen species (ROS). Nanoliposomes (CIR NLPs) encapsulating a near-infrared (NIR) light-sensitive dye, IR780, and a bioactive chlorophyll-rich fraction of Anthocephalus cadamba (CfAc) were synthesized and characterized. These CIR NLPs, when activated by NIR light, displayed localized synergistic cancer cell death under in vitro and in vivo conditions. We demonstrated a NIR light-mediated release of CfAc in cancer cells. The bioactive CfAc was selective in causing ROS generation (leading to autophagic cell death) in cancer cells, while normal healthy cells were unaffected. An increase in the intracellular ROS leading to enhanced lipidation of microtubule-associated protein light chain 3 (LC3-II) was observed only in cancer cells, while normal cells showed no increase in either ROS or LC3-II. In vivo analysis of CIR NLPs in an orthotopic mouse model showed better anti-tumorigenic potential through a combined effect (i.e. via heat and CfAc). We reported for the first time induction of selective and localized, bioactive phyto fraction-mediated autophagic cancer cell death through an NIR light trigger. The synergistic activation of ROS-mediated autophagy by light-triggered nanoliposomes can be a useful strategy for enhancing the anticancer potential of combinational therapies.

Development of label-free gold nanoparticle based rapid colorimetric assay for clinical/point-of-care screening of cervical cancer.

Cervical cancer is the fourth largest cancer, affecting women across the globe. Rapid screening is of vital importance for diagnosis and treatment of the disease, especially in developing countries with high risk populations. In this paper, we report a simple, novel and rapid approach for qualitative screening of cervical cancer. A label-free colorimetric technique ("C-ColAur") involving the in situ formation of gold nanoparticles (Au NPs) in the presence of clinical samples is demonstrated. The as-formed Au NPs, owing to the sample composition produced a characteristic color that can be used for the qualitative detection of malignancy. We demonstrated the proof of principle using clinical samples (cervical fluid) collected from both cancer affected and healthy individuals. The results of the detection technique, "C-ColAur" when compared with those of the existing conventional diagnostic procedures (i.e. Pap smear or biopsy), showed 96.42% sensitivity. With the detection time less than a minute and with no/minimal sample processing requirements, the proposed technique shows great potential for point-of-care as well as clinical screening of cervical cancer.

The "nano to micro" transition of hydrophobic curcumin crystals leading to in situ adjuvant depots for Au-liposome nanoparticle mediated enhanced photothermal therapy.

Photothermal therapy (PTT) is emerging as a promising treatment for skin cancer. Plasmon-resonant gold-coated liposome nanoparticles (Au Lipos NPs) specifically absorb Near Infra-Red (NIR) light resulting in localized hyperthermia (PTT). In the current study, curcumin (a hydrophobic anticancer agent) was entrapped in Au Lipos NPs as nanocrystals to act as an adjuvant for the PTT of melanoma. NIR light irradiation on Au Lipos Cur NPs triggered the release of curcumin nanocrystals which coalesce to form curcumin microcrystals (CMCs). An in situ"nano to micro" transition in the crystal state of curcumin was observed. This in situ transition leads to the formation of CMCs. These CMCs exhibited sustained release of curcumin for a prolonged duration (>10 days). The localized availability of curcumin aids in enhancing PTT by inhibiting the growth and mobility of cancer cells that escape PTT. In the in vitro modified scratch assay, the Au Lipos Cur NP + Laser group showed >1.5 fold enhanced therapeutic coverage when compared with the Au Lipos NP + Laser group. In vivo PTT studies performed in a B16 tumor model using Au Lipos Cur NPs showed a significant reduction of the tumor volume along with the localized release of curcumin in the tumor environment. It was observed that the localized release of curcumin enables an immediate adjuvant effect resulting in the enhancement of PTT.

Chlorophyll rich biomolecular fraction of A. cadamba loaded into polymeric nanosystem coupled with Photothermal Therapy: A synergistic approach for cancer theranostics.

Development of multifunctional biodegradable nanomaterials to encapsulate hydrophobic drugs and their triggered release in cancer theranostics is a challenge. In the current study, we report the encapsulation of potent anticancer - chlorophyll rich biomolecular fraction from the plant Anthocephalus cadamba into a polymeric nanosystem. The biomolecular fraction was combined with an NIR dye IR-780 to make it photo-thermally active. It was evaluated for its combinatorial (biomolecular extract and photothermal mediated) synergistic cytotoxicity in skin cancer cells. The inherent fluorescence of chlorophyll in the fraction was deployed to understand the cellular uptake and drug release. Cellular uptake of hydrophobic CFAc was enhanced with the aid of nanoformulation. It was observed that photo stability of IR-780 improved when incorporated with CFAc in polymeric nanosystem, which resulted in enhanced photothermal transduction efficiency. The combinational approach exhibited synergistic cytotoxicity which can be applied for skin cancer theranostics.