Folate Receptor Positive Cancer Research Articles

Further analysis of phase III, single-dose, open-label study to investigate the efficacy of pafolacianine sodium injection (OTL38) for intraoperative imaging during cytoreductive surgery of folate receptor-positive ovarian cancer (NCT03180307)

Further analysis of phase III, single-dose, open-label study to investigate the efficacy of pafolacianine sodium injection (OTL38) for intraoperative imaging during cytoreductive surgery of folate receptor-positive ovarian cancer (NCT03180307)

Targeted Chemo-Phototherapy in Red Light with Novel Doxorubicin and Iron(III) Complex-Functionalized Gold Nanoconjugate (Dox-Fe@FA-AuNPs).

The anticancer efficacy of doxorubicin, an anthracycline-based and FDA-approved chemotherapeutic drug, is significantly hindered by acquired chemoresistance and severe side effects despite its potent anticancer properties. To overcome these challenges, we developed an innovative therapeutic formulation that integrates targeted chemotherapy and phototherapy within a single platform using gold nanoparticles (AuNPs). This novel nanoconjugate, designated as Dox-Fe@FA-AuNPs, is co-functionalized with folic acid, doxorubicin, and an iron(III)-phenolate/carboxylate complex, enabling cancer-specific drug activation. Here, we report the synthesis, characterization, and comprehensive physico-chemical and biological evaluations of Dox-Fe@FA-AuNPs. The nanoconjugate exhibited excellent solubility, stability, and enhanced cellular uptake in folate receptor-positive cancer cells. The nanoconjugate was potently cytotoxic against HeLa and MDA-MB-231 cancer cells (HeLa: 105.5±16.52 μg mL-1; MDA-MB-231: 112.0±12.31 μg mL-1; MDA-MB-231 (3D): 156.31±19.35 μg mL-1) while less cytotoxic to the folate(-) cancer cells (MCF-7, A549 and HepG2). The cytotoxicity was attributed to the pH-dependent release of doxorubicin, which preferentially occurs in the acidic tumor microenvironment. Additionally, under red light irradiation, the nanoconjugate generated ROS, inducing caspase-3/7-dependent apoptosis with a photo-index (PI) >50, and inhibited cancer cell migration. Our findings underscore the potential of Dox-Fe@FA-AuNPs as a highly effective and sustainable platform for targeted chemo-phototherapy.

Therapeutic effect of F127-folate@PLGA/CHL/IR780 nanoparticles on folate receptor-expressing cancer cells.

Theragnostic platforms, which integrate therapeutic and diagnostic capabilities, have gained significant interest in drug research because of to their potential advantages. This study reports the development of a novel multifunctional nanoparticle carrier system based on poly(ᴅ,ʟ-lactic-co-glycolic acid) (PLGA) for the targeted delivery of the chemotherapeutic agent chlorambucil (CHL) and the imaging agent IR780. The approach in this study incorporates Pluronic F127-folate onto the PLGA nanoparticles, which enables targeted delivery to folate receptor-expressing cancer cells. The F127-folate@PLGA/CHL/IR780 nanoparticles were formulated using a nanoprecipitation technique, resulting in small size, high homogeneity, and negative surface charge. Importantly, the folate-targeted nanoparticles demonstrated enhanced uptake and cytotoxicity in folate receptor-positive cancer cell lines (MCF-7 and HepG-2) compared to folate receptor-negative cells (HEK 293). Additionally, the F127-folate@PLGA/CHL/IR780 nanoparticles exhibited a lower IC50 value against cancer cells than non-targeted F127@PLGA/CHL/IR780 nanoparticles. These findings suggest that the developed F127-folate@PLGA/CHL/IR780 nanoparticles hold promise as a theragnostic system for targeted cancer therapy and diagnosis, leveraging the advantages of PLGA, folate targeting, and the integration of therapeutic and imaging agents.

Development of folate-conjugated polypyrrole nanoparticles incorporated with nitrogen-doped carbon quantum dots for targeted bioimaging and photothermal therapy

PPy nanoparticles are widely employed as PTT agents, because of their exceptional near-infrared absorption properties. Nonetheless, the efficacy of PTT with PPy nanoparticles is hindered by a challenge, specifically, a lack of precise targeting. In this study, a PTT imaging agent was developed by combining NCQDs having bright green fluorescent properties with PPy nanoparticles along with the masking of folic acid to overcome the challenge of targeting. The synthesized PPy:NCQDs:FA nanocomposite, characterized by extraordinary photothermal property, was utilized for imaging of folate receptor positive (FA+) MCF-7 cancer cells through the emission of green fluorescence by NCQDs incorporated within the nanocomposite. Additionally, these nanoparticles demonstrated a good level of cell viability, exceeding 82 %, even at a concentration of 600 μg mL−1. Even the in vivo toxicity inspection of the nanocomposite exemplified no observed acute toxicity at experimental dosages of 1 and 3 mg per kg body weight. By subjecting MCF-7 cells, inoculated with 100 μg mL−1 of nanocomposite, to NIR laser irradiation for 5 min, a significant decline in cell viability was witnessed, establishing the photothermal therapeutic potency of the nanocomposite. The death of cancer cells induced by nanocomposite was verified through MTT assay, imaging of cells by NCQDs alone, with nanocomposite, and by live/dead cell Calcein AM/PI staining assay. Quantification of induced apoptosis post-laser treatment is conducted through staining with Annexin V-FITC/PI. These findings establish potential use of PPy:NCQDs:FA nanocomposite as versatile theranostic agents, capable of targeted bioimaging and treatment for cancer cells exhibiting folate receptors.

Targeted delivery and apoptosis induction of CDK-4/6 inhibitor loaded folic acid decorated lipid-polymer hybrid nanoparticles in breast cancer cells

Targeted drug delivery is an advanced approach for active targeting of tumor that can enhance the concentration of the drug at the site of action and reduce the off-target toxicity and non-specific effects of the drug. Folate receptors (FR) are membrane-bound surface proteins, over-expressed in numerous solid tumors, folate and folate conjugates bind to FR with higher affinity. In the present investigation, we fabricated Folic acid (FA) decorated Palbociclib loaded lipid-polymer hybrid nanoparticles (FA-PLPHNPs) using quality by design (QbD) approach and evaluated its anti-cancer activity in folate receptor-positive breast cancer cell lines. 1HNMR, ATR-FTIR spectroscopic techniques confirmed the formation of DSPE-PEG-FA ligand. The optimized FA-PLPHNPs formulation exhibited 143.36 ± 5.24 nm, 0.172 ± 0.004, −16.84 ± 0.27 mV, and 93.12 ± 0.43 % of particle size, PDI, zeta potential and % entrapment efficiency, respectively. The FA-PLPHNPs exhibited an approximately 9, 11-fold reduction in IC50 values than free Palbociclib in MCF-7 and MDA-MB-231 cells at 48 h. The role of FA in targeting breast cancer was studied by means of a receptor-blocking assay, and concluded that FA-PLPHNPs were internalized into MCF-7 and MDA-MB-231 cells by folate receptor-mediated endocytosis. FA-PLPHNPs showed higher anti-cancer efficiency and caused enhanced reactive oxygen species generation, apoptosis (Acridine orange/ ethidium bromide dual staining and Annexin V/PI staining), reduced cell migration, and colony formation. Thus, the fabricated Palbociclib-loaded FA-conjugated lipid polymer hybrid nanoparticles could act as a potential nanocarrier for the treatment of breast cancer.

A pH-responsive bi-MIL-88B MOF coated with folic acid-conjugated chitosan as a promising nanocarrier for targeted drug delivery of 5-Fluorouracil.

Cancer has remained one of the leading causes of death worldwide, with a lack of effective treatment. The intrinsic shortcomings of conventional therapeutics regarding tumor specificity and non-specific toxicity prompt us to look for alternative therapeutics to mitigate these limitations. In this regard, we developed multifunctional bimetallic (FeCo) bi-MIL-88B-FC MOFs modified with folic acid-conjugated chitosan (FC) as drug delivery systems (DDS) for targeted delivery of 5-Fluorouracil (5-FU). The bi-MIL-88B nanocarriers were characterized through various techniques, including powder X-ray diffraction, scanning electron microscopy, energy-dispersive X-ray, thermogravimetric analysis, and Fourier transform infrared spectroscopy. Interestingly, 5-FU@bi-MIL-88B-FC showed slower release of 5-FU due to a gated effect phenomenon endowed by FC surface coating compared to un-modified 5-FU@bi-MIL-88B. The pH-responsive drug release was observed, with 58% of the loaded 5-FU released in cancer cells mimicking pH (5.2) compared to only 24.9% released under physiological pH (5.4). The in vitro cytotoxicity and cellular internalization experiments revealed the superiority of 5-FU@bi-MIL-88B-FC as a highly potent targeted DDS against folate receptor (FR) positive SW480 cancer cells. Moreover, due to the presence of Fe and Co in the structure, bi-MIL-88B exhibited peroxidase-like activity for chemodynamic therapy. Based on the results, 5-FU@bi-MIL-88B-FC could serve as promising candidate for smart DDS by sustained drug release and selective targeting.

Targeted PEGylated Chitosan Nano-complex for Delivery of Sodium Butyrate to Prostate Cancer: An In Vitro Study.

Introduction: Cancer remains a challenging issue against human health throughout the world; As a result, introducing novel approaches would be beneficial for cancer treatment. In this research, sodium butyrate (Sb) is one of the effective anti-cancer therapeutics (also a potent survival factor for normal cells) that was used for prostate cancer suppression in the platform of modified chitosan (CS) nano-complex (polyethylene glycol (PEG)-folic acid (FA)-Sb-CS). Methods: Different analytical devices including Fourier transform infrared, dynamic light scattering, high-performance liquid chromatography, scanning electron microscopy, and transmission electron microscopy were applied for the characterization of synthetics. On the other hand, biomedical tests including cell viability assay, molecular and functional assay of apoptosis/autophagy pathways, and cell cycle arrest analysis were potentially implemented on human PC3 (folate receptor-negative prostate cancer) and DU145 (folate receptor-positive prostate cancer) and HFF-1 normal cell lines. Results: The quality of the syntheses was effectively verified, and the size range from 140 to 170 nm was determined for the PEG-CS-FA-Sb sample. Also, 75 ± 5% of drug entrapment efficiency with controlled drug release manner (Sb release of 54.21% and 74.04% for pHs 7.4 and 5.0) were determined for nano-complex. Based on MTT results, PEG-CS-FA-Sb has indicated 72.07% and 33.53% cell viability after 24 h of treatment with 9 mM on PC3 and DU145 cell lines, respectively, which is desirable anti-cancer performance. The apoptotic and autophagy genes overexpression was 15-fold (caspase9), 2.5-fold (BAX), 11-fold (ATG5), 2-fold (BECLIN1), and 3-fold (mTORC1) genes in DU145 cancer cells. More than 50% of cell cycle arrest and 45.05% of apoptosis were obtained for DU145 cancer cells after treatment with nano-complex. Conclusion: Hence, the synthesized Sb-loaded nano-complex could specifically suppress prostate cancer cell growth and induce apoptosis and autophagy in the molecular and cellular phases.

Functionalized Graphitic Carbon Nitride Nanomaterials for Electrochemiluminescent Detection of Cancer Cells

Biosensors capable of detecting cancer cell quantity is significant for cancer pathological investigation and prognosis. Herein, a facile electrochemiluminescent (ECL) biosensor is developed for cancer cell detection by comprehensively utilizing the features of functionalized graphitic carbon nitride (g-CN) nanomaterials like well film-forming capability and functionalization level tunability. The solid-state ECL biosensor is fabricated via a simple dropping-drying method by subsequent deposition of g-CN nanosheets/graphene oxide nanocomposites (CNNS/GO) as ECL emitter, folate functionalized g-CN quantum dots (FA-CNQDs) as cancer cell capture agent, and bull serum albumin (BSA) as blocker to prevent nonspecific binding on glassy carbon electrodes (GCEs). The strong and stable ECL emission of CNNS/GO along with the tunability of FA content in FA-CNQDs endow the ECL biosensor with competitive sensitivity, which is able to detect folate receptor-positive cancer cells (HepG2) in the concentration range of 102 − 104 cells ml−1 under optimal condition. Additionally, the proposed ECL biosensor shows high specificity, reproducibility and long-term stability as well as good reliability towards serum sample detection.

Synthesis, optical, structural and biocompatibility assessment of red-emitting CuInS[formula omitted]-ZnS quantum dots conjugated to folic acid

Bioconjugation of nanoparticles is a hot topic of research for a wide range of biological applications, particularly in cancer diagnosis and treatment. In this study, we report the synthesis of glutathione capped CuInS2/ZnS quantum dots (QDs) in an aqueous medium followed by folic acid (FA) modification to produce CIS-ZnS/FA conjugates. The as-synthesized QDs were small, with an average particle diameter of 2.3 nm, and emit in the red region, which was retained even after conjugation with FA. The formation of the conjugates was investigated by ultraviolet–visible (UV–Vis) absorption, photoluminescence (PL) and Fourier transform infrared (FTIR) spectroscopy. The conjugate were then analyzed for their cytotoxicity against both folate receptor (FR) positive (HeLa) and FR negative (A549, C26) cancer cell lines. The results of this study revealed the highly biocompatible nature of the CIS-ZnS/FA conjugates towards both FR positive and negative cancer cell lines and thus they are of potential use in biological applications.

Folate functionalized gold-coated magnetic nanoparticles effect in combined electroporation and radiation treatment of HPV-positive oropharyngeal cancer.

The rate of HPV-positive oropharyngeal cancer incidence is increasing, especially in the young population. While these patients show good responses to radiotherapy. The major complication of radiotherapy is normal tissue involvement. Thus, finding an effective treatment method is essential. Multimodal therapy with the lowest side effect could be an effective treatment method. Theranostic gold magnetic core-shell nanostructure was developed as aplatform for multimodal therapy of HPV-positive oropharyngeal cancer. The folate functionalized gold-magnetic core-shell nanostructure has been synthesized in a stepwise approach and characterized with various techniques including TEM, UV-Vis, and FTIR spectroscopy. KB was selected as a host for HPV and folate receptor-positive cancer. HGF as normal cell lines was selected. Both cell lines have been treated with nanoparticles, electric field and radiotherapy, either separately or in combination. Cell viability and apoptosis rate were determined by MTT and flow cytometry assay. In addition, cellular uptake of the nanoparticles was measured by ICP-OES analysis. The average size of folate functionalized gold-magnetic core-shell nanostructure was 13.8 ± 6.4nm. A characteristic plasmonic peak of gold nanoshells was observed in the UV-Vis spectrum. The functionalization of synthesized nanostructure was confirmed with FTIR spectroscopy. None of the treatments alone can cause a significant death in cancerous cells. Combination treatments can increase cancer cell mortality and increase the proportion of apoptotic cells in them. Furthermore, it has been observed that the electric field enhanced the cellular uptake of nanoparticles just in cancerous cells. Based on our findings, we conclude that the combination of folate functionalized nanoparticles and electroporation opens a new way to improve radiation therapy efficacy of HPV-positive cancers.

Nanofabrication of PLGA-PEG-chitosan-folic acid systems for delivery of colchicine to HT-29 cancer cells

This survey was conducted to fabrication of PLGA-based nanosystems modified with PEG, chitosan and folic acid to delivery colchicine to cancer cells and to investigate its antioxidant and pro-apoptotic effects. The dual emulsion-evaporation solvent method was used for loading of colchicine on PEGylated PLGA nanoparticles (COL-PP-NPs) and after surface modification with chitosan and folic acid (COL-PPCF-NPs), the nanoparticles were characterized by DLS, SEM and FTIR methods. The HPLC procedure was used to assess the amount of FA binding and COL loading. Antioxidant capacity (ABTS and DPPH free radical scavenging) and toxicity (MTT) of COL-PPCF-NPs were evaluated and then cell inhibition mechanism was assessed by AO/PI staining, flow cytometry and qPCR assay. COL-PPCF-NPs with a size of 250 nm were synthesized in a stable (zeta potential: +34 mV) and mono-dispersed (PDI: 0.32) manner. FA binding and COL loading were reported to be 55% and 89.5%, respectively. COL-PPCF-NPs showed antioxidant effects by inhibiting the free radicals ABTS (108.07 µg/ml) and DPPH (361.61 µg/ml). The selective toxicity of COL-PPCF-NPs against HT-29 cancer cells (118.5 µg/ml) compared to HFF cells was confirmed by MTT data. Increased apoptotic cells (red color) in AO/PI staining, cell arrest in phase SubG1 and G2-M, and altered expression of apoptosis genes confirmed the occurrence of apoptosis in HT-29 treated cells. The use of PPCF-NPs system for delivery of COL can lead to selective toxicity against cancer cells and induction of apoptosis in these cells by folate-mediated binding mechanism at folate receptor positive HT-29 cancer cells.

Designing of a pH-activatable carbon dots as a luminescent nanoprobe for recognizing folate receptor-positive cancer cells

During recent years, cancer has been recognized as a well-known disorder all over the world. One of the important factors to tackle this problem better than past decades is early diagnosis that takes into practice by state-of-the-art visual equipment for detection cancer cells. Herein, in this research, we synthesized carbon dots with pH-dependent behavior from a green source by hydrothermal method with high quantum yield and blue fluorescence. Folic acid-conjugated carbon dots by an efficient and optimal conjugation method were set upped which determined cancer cells visually. These synthesized and conjugated nanoparticles entered into the cancer cells more comprehensive than normal cells by receptor-mediated endocytosis and could distinguish cancer cells from normal ones by fluorescence imaging. Ultimately, synthesized nanoparticles in this research can be considered as an efficient fluorescent nanoprobe for cancer pre-diagnosis.

Synthesis, Radiolabeling, and Biological Evaluation of 68Ga-Mucin1 and Its Folate Hybrid Peptide Conjugates for the Diagnosis of Ovarian Cancer

Because of our interest in developing new hybrid peptide radioconjugates with suitable biochemical properties for multiple-receptors targeting properties that are overexpressed on many human cancers especially ovarian cancer, we have synthesized 68Ga-NODAGA-MUC1 and 68Ga-NODAGA-MUC1-FA hybrid peptide conjugates using a straightforward and one-step simple reaction. Radiochemical yields were found to be higher than 95% (decay corrected), with a total synthesis time of less than 20 min. Radiochemical purities were always higher than 95% without HPLC purification. In vitro studies on KB cancer cells showed that substantial amounts of the radioconjugates were associated with cell fractions and held great affinities and specificities toward the KB cell line. In vivo characterization in normal female Balb/c mice revealed rapid blood clearance of these radioconjugates with excretion predominantly by the urinary system. Biodistribution studies in nude mice bearing human KB cell line xenografts demonstrated significant tumor uptake and favorable biodistribution profile for 68Ga-NODAGA-MUC1-FA hybrid peptide conjugate compared to the 68Ga-NODAGA-MUC1 peptide monomeric counterpart. The uptake in the tumors was blocked by the excess injection of hybrid peptide, suggesting a receptor-mediated process. These results demonstrate that 68Ga-NODAGA-MUC1-FA hybrid peptide conjugate may be useful as a molecular probe for early detection and staging of folate and MUC1 receptor-positive cancers such as ovarian cancer and their metastasis as well as monitoring tumor response to treatment.

Glycoprotein-based bioimaging of HeLa cancer cells by folate receptor and folate decorated graphene quantum dots

Folate receptor (FR, 38 kDa) is a glycosylphosphatidylinositol glycoprotein which overexpressed on the surface of various cancer cells and has been utilized for wide applications. Folic acid (FA) functionalized nitrogen doped graphene quantum dots wrapped terbium (III) tungstate nanoparticles (Tb2(WO4)3NPs@N-GQDs-FA or Tb-W@GQDs-FA) as a smart nanocomposite was synthesized and used for specific imaging of folate receptor (FR) positive HeLa cancer cells. The mechanism of action is based on the attachment of FA decorated nanomaterials to the FR on the surface of cancer cells. This bioimaging probe emits fluorescence emission at 450 nm upon excitation on 345 nm. Flow cytometry and fluorescence microscopy techniques were applied to evaluate the efficiency of uptake of Tb-W@GQDs-FA to the cancer cells. Also, the selective attachment of Tb-W@GQDs-FA particles towards FR-positive HeLa cancer cells was verified by incubation of Tb-W@GQDs-FA with FR-negative normal cells. The cellular toxicity of the produced Tb-W@GQDs-FA nanocomposite was evaluated and results approved its biocompatible nature at the concentration of about 400 µg/mL. In conclusion, Tb-W@GQDs-FA could be effectively applied for noninvasive bio-imaging of HeLa cancer cells.

Phase 3, randomized, single-dose, open-label study to investigate the safety and efficacy of pafolacianine sodium injection (OTL38) for intraoperative imaging of folate receptor positive ovarian cancer.

5503 Background: Pafolacianine sodium is under investigation as an adjunct to visual inspection and palpation by providing intra-operative imaging of folate receptor positive (FR+) ovarian cancer. Since complete resection (R0) is the strongest predictor of overall survival, methods to enhance detection of lesions are expected to benefit patient outcomes. Methods: For this phase 3, randomized, multicenter, single dose, open-label pivotal trial (NCT03180307), patients with ovarian cancer who were scheduled to undergo cytoreductive surgery were recruited from 11 sites in the US and Netherlands from March 2018 through April 2020. The study objectives were to confirm efficacy and safety of pafolacianine sodium (0.025 mg/kg i.v., ≥1 h prior to imaging) in combination with intraoperative near-infrared fluorescence (NIRF) imaging to detect additional lesions not detected by palpation and normal white light alone. Results: Pafolacianine sodium was administered to 150 total patients (safety analysis set); 109 patients comprised the full analysis set for efficacy analyses. Patients had primarily serous adenocarcinoma (n = 72; 68.6%) and advanced stage disease (n = 83; 76.1%). In 33% of patients (36 of 109), NIRF imaging with pafolacianine sodium identified additional lesions that were not planned for resection and were not detected by normal white light and palpation ( P < 0.001, 95% CI [0.243, 0.427]). Among patients who underwent interval debulking surgery, the rate was higher, at 39.7% of patients (23 of 58; 95% CI [0.270, 0.534]). At the individual lesion level, the accuracy of pafolacianine sodium with NIRF to detect ovarian cancer is reflected by sensitivity of 83% (95% CI [73.9, 89.4]) and a false positive rate of 32.7% (95% CI [25.6, 40.7]). Investigators reported achieving complete resection (R0) in 62.4% (68 of 109) of patients. Drug-related adverse events (AEs) were reported by 30% of patients (45 out of 150). The most frequently reported drug-related AEs were nausea (18.0%), vomiting (5.3%), and abdominal pain (4.7%). Infusion reactions at the time of the procedure were mostly (96%) mild or moderate in severity; 89% resolved within 24 hours of onset. No drug-related serious AEs or deaths were reported. Conclusions: This phase 3 trial of pafolacianine sodium with NIRF imaging met its primary endpoint, intraoperatively identifying additional cancer not planned for resection in a statistically significant number of patients. Therefore, pafolacianine sodium may offer a novel real-time adjunct to current surgical imaging practice in ovarian cancer surgery. Clinical trial information: NCT03180307.

Novel decorated nanostructured lipid carrier for simultaneous active targeting of three anti-cancer agents

Cancer-targeted co-delivery of therapeutic agents has been recognized as an effective strategy for increasing efficacy and reducing side effects of therapeutic agents. In this study, we used methotrexate (MTX) alone as a targeting moiety and chemotherapeutic agent and in combination with docetaxel (DTX) and doxorubicin (DOX) as chemotherapeutic agents to stop cancer cell proliferation with the aid of newly designed nanostructured lipid carriers (NLCs). The physicochemical properties of our designed nanocomplexes were evaluated by DLS, FT-IR spectroscopy, SEM, and TEM. Moreover, the targeting efficiency of the designed and synthesized nanoplatforms was evaluated on the folate receptor (FR) positive human breast cancer cell line (MCF-7) and FR negative human alveolar basal epithelial cells (A549). The NLCs/DTX/DOX/CS and NLCs/DTX/DOX/CS-MTX complexes significantly increased the cell cytotoxicity and the cell apoptosis rate. However, the complexes significantly reduced the capability of colony formation and cell migration. Our results revealed that NLCs/DTX/DOX/CS-MTX had synergistic cytotoxicity, reactive oxygen spaces, autophagy, and the apoptosis induction ability with an enhanced cellular internalization rate in FR-positive cancer cells, thorough MTX recognition capability. We conclude that the NLCs/DTX/DOX/CS-MTX complex is a new promising paradigm for breast cancer-targeted co-delivery.

Folic Acid Functionalized Carbon Dot/Polypyrrole Nanoparticles for Specific Bioimaging and Photothermal Therapy.

Polypyrrole nanoparticles (PPy-NPs) with excellent near-infrared absorption are commonly used as photothermal therapy (PTT) agents; however, PTT using PPy-NPs has a limitation in that it is difficult to maximize their therapeutic effect because of the lack of specific targeting. In this study, to overcome the difficulty of targeting, folic acid functionalized carbon dots (FA-CDs) with bright green fluorescence properties were combined with carboxylated PPy-NPs via the EDC/NHS coupling reaction to yield a PTT imaging agent. The synthesized FA-CD/PPy-NPs with excellent photostability performed folate receptor (FR) positive HeLa cancer cell imaging by green fluorescence signals of FA-CDs and exhibited high cell viability (above 90%) even at 500 μg/mL. The viability of HeLa cells incubated with 200 μg/mL FA-CD/PPy-NPs was dramatically decreased to 25.02 ± 1.85% by NIR laser irradiation, through photothermal therapeutic effects of FA-CD/PPy-NPs with high photothermal conversion efficiency (η = 40.80 ± 1.54%). The cancer cell death by FA-CD/PPy-NPs was confirmed by fluorescence imaging of FA-CDs as well as live/dead cell staining assay (calcein-AM/PI). These results demonstrate that the FA-CD/PPy-NPs can be utilized as multifunctional theranostic agents for specific bioimaging and treatment of FR-positive cancer cells.

Near-Infrared Fluorescent Probe Activated by Nitroreductase for In Vitro and In Vivo Hypoxic Tumor Detection.

Tumor hypoxia is correlated with increased resistance to chemotherapy and poor overall prognoses across a number of cancer types. We present here a cancer cell-selective and hypoxia-responsive probe (fol-BODIPY) designed on the basis of density functional theory (DFT)-optimized quantum chemical calculations. The fol-BODIPY probe was found to provide a rapid fluorescence "off-on" response to hypoxia relative to controls, which lack the folate or nitro-benzyl moieties. In vitro confocal microscopy and flow cytometry analyses, as well as in vivo near-infrared optical imaging of CT26 solid tumor-bearing mice, provided support for the contention that fol-BODIPY is more readily accepted by folate receptor-positive CT26 cancer cells and provides a superior fluorescence "off-on" signal under hypoxic conditions than the controls. Based on the findings of this study, we propose that fol-BODIPY may serve as a tumor-targeting, hypoxia-activatable probe that allows for direct cancer monitoring both in vitro and in vivo.

­­A Randomized Phase 3 Study of Pafolacianine Injection (OTL38) for Intraoperative Imaging of Folate Receptor Positive Ovarian Cancer

­­A Randomized Phase 3 Study of Pafolacianine Injection (OTL38) for Intraoperative Imaging of Folate Receptor Positive Ovarian Cancer

Functional titanium dioxide nanoparticle conjugated with phthalocyanine and folic acid as a promising photosensitizer for targeted photodynamic therapy in vitro and in vivo

Photodynamic therapy (PDT) is a promising cancer treatment that can be implemented using various agents. The conventional photosensitizer Al (III) phthalocyanine chloride tetrasulfonic acid (Pc) has limitations of selectivity in tumor targeting, low affinity to cancer cells, and low two-photon absorption. This study presents a novel photosensitizer FA-TiO2-Pc, which has the TiO2 nanoparticle conjugated with a tumor targeting agent of folic acid (FA), and Pc. FA-TiO2-Pc possessed high targeted photodynamic therapeutic activity and excellent biocompatibility. This promising photosensitizer showed high therapeutic drug efficiency in vitro at a low concentration dose and short incubation time under one-photon excitation (OPE). In vivo, when treated with a low dose of FA-TiO2-Pc and low light irradiation, the tumor growth was depressed in mice bearing HeLa xenograft tumors with minimal side effects. In addition, the two-photon absorption of FA-TiO2-Pc was also enhanced compared to Pc, proving that FA-TiO2-Pc system has a great potential to be used for the therapy of the folate receptor positive cancer cells in both OPE-PDT and two-photon excitation (TPE)-PDT agents.