pH‐sensitive carbon quantum dots−doxorubicin nanoparticles for tumor cellular targeted drug delivery

A kind of pH‐responsive carbon quantum dots?doxorubicin nanoparticles drug delivery platform (D‐Biotin/DOX‐loaded mPEG‐OAL/N‐CQDs) was designed and synthesized. The system consists of fluorescent carbon dots as cross‐linkers, and D‐Biotin worked as targeting groups, which made the system have a pH correspondence, doxorubicin hydrochloride (DOX) as the target drug, oxidized sodium alginate (OAL) as carrier materials. Ultraviolet (UV)‐Vis spectrum showed that the drug‐loading rate of DOX is 10.5%, and the drug release in vitro suggested that the system had a pH response and tumor cellular targeted, the drug release rate is 65.6% at the value of pH is 5.0, which is much higher than that at the value of pH is 7.4. The cytotoxicity test and laser confocal fluorescence imaging showed that the synthesized drug delivery system has high cytotoxicity to cancer cells, and the drug‐loaded nanoparticles could enter the cells through endocytosis.     

Hyperbranched poly (amine‐ester)‐poly (lactide‐co‐glycolide) copolymer and their nanoparticles as paclitaxel delivery system

A new hyperbranched poly (amine‐ester)‐poly (lactide‐co‐glycolide) copolymer (HPAE‐co‐PLGA) was synthesized by ring‐opening polymerization of D , L ‐lactide (DLLA) glycolid and branched poly (amine‐ester) (HPAE‐OHs) with Sn(Oct)₂ as catalyst. The chemical structures of copolymers were determined by FT‐IR, ¹H‐NMR(¹³C NMR), TGA and their molecular weights were determined by gel permeation chromatography (GPC). Paclitaxel‐loaded copolymer nanoparticles were prepared by the nanoprecipitation method. Their physicochemical characteristics, e.g. morphology and nanoparticles size distribution were then evaluated by means of fluorescence spectroscopy, environmental scanning electron microscopy (ESEM), and dynamic light scattering (DLS). Paclitaxel‐loaded nanoparticles assumed a spherical shape and have unimodal size distribution. It was found that the chemical composition of the nanoparticles was a key factor in controlling nanoparticles size, drug‐loading content, and drug release behavior. As the molar ratio of DL ‐lactide/glycolide to HPAE increased, the nanoparticles size and drug‐loading content increased, and the drug release rate decreased. The antitumor activity of the paclitaxel‐loaded HPAE‐co‐PLGA nanoparticles against human liver cancer H7402 cells was evaluated by 3‐(4, 5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) method. The paclitaxel‐loaded HPAE‐co‐PLGA nanoparticles showed comparable anticancer efficacy with the free drug. Copyright © 2010 John Wiley & Sons, Ltd.     

Stabilizer‐Free Poly(lactide‐co‐glycolide) Nanoparticles Conjugated with Quantum Dots as a Potential Carrier Applied in Human Mesenchymal Stem Cells

We report that human mesenchymal stem cells (hMSCs) were successfully labeled with poly(lactide‐co‐glycolide) nanoparticles (PLGA NPs) surface‐conjugated quantum dots (QDs) (PLGA‐QD NPs) via endocytosis pathway. These NPs were not toxicity even treated with PLGA‐QD NPs at high concentrations for at least four weeks. Besides, PLGA‐QD NPs‐labeled hMSCs did not change their proliferation and differentiation capability toward the cell fates of adipocytes, osteocytes, and chrondrocytes. It's known that PLGA has been widely employed to act as delivery carrier which encapsulates drugs and releases them under a controlled way. Currently, we have also demonstrated that FITC‐loaded PLGA‐QD NPs degraded in hMSCs to achieve intracellular release of FITC. The aim of this research is to investigate viability, proliferation and differentiation capability and the potential for gene delivery of MSCs labeled with PLGA‐QD NPs. In addition to PLGA‐QD NPs, QDs alone were used to serve as a control set for comparison.     

Stem cell membrane vesicle–coated nanoparticles for efficient tumor‐targeted therapy of orthotopic breast cancer

Nanoparticles‐based drug delivery strategies have been widely researched for cancer therapy. However, most of them are expected to accumulate in tumor sites via the enhanced permeability and retention (EPR) effect, which is insufficient to deliver the loaded drug into tumors. Cell membrane–camouflaged nanoparticles have obtained much attention for their excellent stability and long blood circulation and reduced the macrophage cells uptake in drug delivery. Herein, bone marrow–derived mesenchymal stem cell membrane vesicle (SCV)–coated paclitaxel (PTX)–loaded poly (lactide‐co‐glycolide) (PLGA) nanoparticles (SCV/PLGA/PTX) were fabricated as the efficient orthotopic breast cancer–targeted drug delivery system. The SCV/PLGA/PTX showed excellent stability, more controlled PTX release, and more effective antitumor effect in vitro. After administration in vivo, SCV/PLGA/PTX exhibited the long‐term retention and enhanced accumulation at tumor sites due to the immune escape and mesenchymal stem cell–mimicking cancer‐targeting capacity. As expected, the SCV/PLGA/PTX could significantly suppress the primary tumor growth by increased apoptosis and necrosis areas within tumor tissues and attenuated the toxic side effects of PTX in 4T1 orthotopic breast cancer model. The study indicated the mesenchymal stem cell membrane coating strategy was highly efficient for targeted drug delivery, which provided a new insight for precise and effective breast cancer treatment.     

Dendritic Polyglycerol‐Derived Nano‐Architectures as Delivery Platforms of Gemcitabine for Pancreatic Cancer

Dendritic polyglycerol‐co‐polycaprolactone (PG‐co‐PCL)‐derived block copolymers are synthesized and explored as nanoscale drug delivery platforms for a chemotherapeutic agent, gemcitabine (GEM), which is the cornerstone of therapy for pancreatic ductal adenocarcinoma (PDAC). Current treatment strategies with GEM result in suboptimal therapeutic outcome owing to microenvironmental resistance and rapid metabolic degradation of GEM. To address these challenges, physicochemical and cell‐biological properties of both covalently conjugated and non‐covalently stabilized variants of GEM‐containing PG‐co‐PCL architectures have been evaluated. Self‐assembly behavior, drug loading and release capacity, cytotoxicity, and cellular uptake properties of these constructs in monolayer and in spheroid cultures of PDAC cells are investigated. To realize the covalently conjugated carrier systems, GEM, in conjunction with a tertiary amine, is attached to the polycarbonate block grafted from the PG‐co‐PCL core. It is observed that pH‐dependent ionization properties of these amine side‐chains direct the formation of self‐assembly of block copolymers in the form of nanoparticles. For non‐covalent encapsulation, a facile “solvent‐shifting” technique is adopted. Fabrication techniques are found to control colloidal and cellular properties of GEM‐loaded nanoconstructs. The feasibility and potential of these newly developed architectures for designing carrier systems for GEM to achieve augmented prognosis for pancreatic cancer are reported.     

Biocompatible Triplex Ag@SiO2@mTiO2 Core–Shell Nanoparticles for Simultaneous Fluorescence‐SERS Bimodal Imaging and Drug Delivery

Herein, we report the synthesis of biocompatible triplex Ag@SiO₂@mTiO₂ core–shell nanoparticles (NPs) for simultaneous fluorescence‐surface‐enhanced Raman scattering (F‐SERS) bimodal imaging and drug delivery. Stable Raman signals were created by typical SERS tags that were composed of Ag NPs for optical enhancement, a reporter molecule of 4‐mercaptopyridine (4‐Mpy) for a spectroscopic signature, and a silica shell for protection. A further coating of mesoporous titania (mTiO₂) on the SERS tags offered high loading capacity for a fluorescence dye (flavin mononucleotide) and an anti‐cancer drug (doxorubicin (DOX)), thereby endowing the material with fluorescence‐imaging and therapeutic functions. The as‐prepared F‐SERS dots exhibited strong fluorescence when excited by light at 460 nm whilst a stable, characteristic 4‐Mpy SERS signal was detected when the excitation wavelength was changed to longer wavelength (632.8 nm), both in solution and after incorporation inside living cells. Their excellent biocompatibility was demonstrated by low cytotoxicity against MCF‐7 cells, even at a high concentration of 100 μg mL^?1. In vitro cell cytotoxicity confirmed that DOX‐loaded F‐SERS dots had a comparable or even greater therapeutic effect compared with the free drug, owing to the increased cell‐uptake, which was attributed to the possible endocytosis mechanism of the NPs. To the best of our knowledge, this is the first proof‐of‐concept investigation on a multifunctional nanomedicine that possessed a combined capacity for fast and multiplexed F‐SERS labeling as well as drug‐loading for cancer therapy.     

Effect of the Folate Ligand Density on the Targeting Property of Folated‐Conjugated Polymeric Nanoparticles

Targeted drug delivery systems have attracted increasing attention due to their ability for delivering anticancer drugs selectively to tumor cells. Folic acid (FA)‐conjugated targeted block copolymers, FA‐Pluronic‐polycaprolactone (FA‐Pluronic‐PCL) are synthesized in this study. The anticancer drug paclitaxel (PTX) is loaded in FA‐Pluronic‐PCL nanoparticles by nanoprecipitation method. The in vitro release of PTX from FA‐Pluronic‐PCL nanoparticles shows slow and sustained release behaviors. The effect of FA ligand density of FA‐Pluronic‐PCL nanoparticles on their targeting properties is examined by both cytotoxicity and fluorescence methods. It is shown that FA‐Pluronic‐PCL nanoparticles indicated better targeting ability than non‐targeted PCL‐Pluronic‐PCL nanoparticles. Furthermore, FA‐F127‐PCL nanoparticle with 10% FA molar content has more effective antitumor activity and higher cellular uptake than those with 50% and 91% FA molar content. These results prove that FA‐F127‐PCL nanoparticle with 10% FA molar content can be a better candidate as the drug carrier in targeted drug delivery systems.     

Synthesis of Polynucleotide Modified Gold Nanoparticles as a High Potent Anti‐Cancer Drug Carrier

Gold nanoparticles have been developed for the photoacoustic imaging, delivery of genes and laser induced photothermal therapy. In this study, we have developed oligonucleotide conjugated gold nanoparticles as the carrier for simultaneous DNA and anti‐cancer nucleoside delivery. The polynucleotidenanoparticle complex presented higher capacity in carrying 5‐FU anti‐cancer compounds than the original gold particles. The hydrodynamic size of the gold nanoparticles increased from 25 to 35 nm with an increase in the negative surface charge from ?9.58 to 21.66 mV after polynucleotide conjugation and drug loading. A positive association between environmental pH and drug release was observed in PBS, which implied their potential use in the controlled localized drug release in the lower GI tract. The MTT assay revealed dose dependent cytotoxicity to colon cancer cell line than free compounds. These results suggest the potential use of this new polynucleotide‐gold nanoparticles complex as the environmental controlled anti‐cancer nanocapsule, especially suitable for per oral colon cancer chemotherapy.     

Carboplatin‐Complexed and cRGD‐Conjugated Unimolecular Nanoparticles for Targeted Ovarian Cancer Therapy

Platinum‐based chemotherapy has been widely used to treat cancers including ovarian cancer; however, it suffers from dose‐limiting toxicity. Judiciously designed drug nanocarriers can enhance the anticancer efficacy of platinum‐based chemotherapy while reducing its systemic toxicity. Herein the authors report a stable and water‐soluble unimolecular nanoparticle constructed from a hydrophilic multi‐arm star block copolymer poly(amidoamine)‐b‐poly(aspartic acid)‐b‐poly(ethylene glycol) (PAMAM‐PAsp‐PEG) conjugated with both cRGD (cyclo(Arg‐Gly‐Asp‐D‐Phe‐Cys) peptide and cyanine5 (Cy5) fluorescent dye as a platinum‐based drug nanocarrier for targeted ovarian cancer therapy. Carboplatin is complexed to the poly(aspartic acid) inner shell via pH‐responsive ion–dipole interactions between carboplatin and the carboxylate groups of poly(aspartic acid). Based on flow cytometry and confocal laser scanning microscopy analyses, cRGD‐conjugated unimolecular nanoparticles exhibit much higher cellular uptake by ovarian cancer cells overexpressing α_vβ₃ integrin than nontargeted (i.e., cRGD‐lacking) ones. Carboplatin‐complexed cRGD‐conjugated nanoparticles also exhibit higher cytotoxicity than nontargeted nanoparticles as well as free carboplatin, while empty unimolecular nanoparticles show no cytotoxicity. These results indicate that stable unimolecular nanoparticles made of individual hydrophilic multi‐arm star block copolymer molecules conjugate with tumor‐targeting ligands and dyes (i.e., PAMAM‐PAsp‐PEG‐cRGD/Cy5) are promising nanocarriers for platinum‐based anticancer drugs for targeted cancer therapy.

     

Self‐Assembled Fluorescent Organic Nanoparticles for Live‐Cell Imaging

Fluorescent, cell‐permeable, organic nanoparticles based on self‐assembled π‐conjugated oligomers with high absorption cross‐sections and high quantum yields have been developed. The nanoparticles are generated with a tuneable density of amino groups for charge‐mediated cellular uptake by a straightforward self‐assembly protocol, which allows for control over size and toxicity. The results show that a single amino group per ten oligomers is sufficient to achieve cellular uptake. The non‐toxic nanoparticles are suitable for both one‐ and two‐photon cellular imaging and flow cytometry, and undergo very efficient cellular uptake.     

Integrated Hollow Mesoporous Silica Nanoparticles for Target Drug/siRNA Co‐Delivery

A hollow mesoporous silica nanoparticle (HMSNP) based drug/siRNA co‐delivery system was designed and fabricated, aiming at overcoming multidrug resistance (MDR) in cancer cells for targeted cancer therapy. The as‐prepared HMSNPs have perpendicular nanochannels connecting to the internal hollow cores, thereby facilitating drug loading and release. The extra volume of the hollow core enhances the drug loading capacity by two folds as compared with conventional mesoporous silica nanoparticles (MSNPs). Folic acid conjugated polyethyleneimine (PEI‐FA) was coated on the HMSNP surfaces under neutral conditions through electrostatic interactions between the partially charged amino groups of PEI‐FA and the phosphate groups on the HMSNP surfaces, blocking the mesopores and preventing the loaded drugs from leakage. Folic acid acts as the targeting ligand that enables the co‐delivery system to selectively bind with and enter into the target cancer cells. PEI‐FA‐coated HMSNPs show enhanced siRNA binding capability on account of electrostatic interactions between the amino groups of PEI‐FA and siRNA, as compared with that of MSNPs. The electrostatic interactions provide the feasibility of pH‐controlled release. In vitro pH‐responsive drug/siRNA co‐delivery experiments were conducted on HeLa cell lines with high folic acid receptor expression and MCF‐7 cell lines with low folic acid receptor expression for comparison, showing effective target delivery to the HeLa cells through folic acid receptor meditated cellular endocytosis. The pH‐responsive intracellular drug/siRNA release greatly minimizes the prerelease and possible side effects of the delivery system. By simultaneously delivering both doxorubicin (Dox) and siRNA against the Bcl‐2 protein into the HeLa cells, the expression of the anti‐apoptotic protein Bcl‐2 was successfully suppressed, leading to an enhanced therapeutic efficacy. Thus, the present multifunctional nanoparticles show promising potentials for controlled and targeted drug and gene co‐delivery in cancer treatment.     

Stimuli‐responsive zein‐based nanoparticles as a potential carrier for ellipticine: Synthesis,release, and in vitro delivery

In the present research, we have investigated a drug delivery system based on the pH‐responsive behaviors of zein colloidal nanoparticles coated with sodium caseinate (SC) and poly ethylene imine (PEI). These systematically designed nanoparticles were used as nanocarriers for encapsulation of ellipticine (EPT), as an anticancer drug. SC and PEI coatings were applied through electrostatic adsorption, leading to the increased size and improved polydispersity index of nanoparticles as well as sustained release of drug. Physicochemical characteristics such as hydrodynamic diameter, size distribution, zeta potential and morphology of nanoparticles prepared using different formulations and conditions were also determined. Based on the results, EPT was encapsulated into the prepared nanoparticles with a high drug loading capacity (5.06%) and encapsulation efficiency (94.8%) under optimal conditions. in vitro experiments demonstrated that the release of EPT from zein‐based nanoparticles was pH sensitive. When the pH level decreased from 7.4 to 5.5, the rate of drug release was considerably enhanced. The mechanism of pH‐responsive complexation in the drug encapsulation and release processes was extensively investigated. The pH‐dependent electrostatic interactions and drug state were hypothesized to affect the release profiles. Compared to the EPT‐loaded zein/PEI nanoparticles, the EPT‐loaded zein/SC nanoparticles exhibited a better drug sustained‐release profile, with a smaller initial burst release and longer release period. According to the results of in vitro cytotoxicity experiments, drug‐free nanoparticles were associated with a negligible cytotoxicity, whereas the EPT‐loaded nanoparticles displayed a high toxicity for the cancer cell line, A549. Our findings indicate that these pH‐sensitive protein‐based nanoparticles can be used as novel nanotherapeutic tools and potential antineoplastic drug carriers for cancer chemotherapy with controlled release.     

pH‐responsive near‐infrared emitting conjugated polymer nanoparticles for cellular imaging and controlled‐drug delivery

In this article, pH‐responsive near‐infrared emitting conjugated polymer nanoparticles (CPNs) are prepared, characterized, and their stabilities are investigated under various conditions. These nanoparticles have capacity to be loaded with water insoluble, anticancer drug, camptothecin (CPT), with around 10% drug loading efficiency. The in vitro release studies demonstrate that the release of CPTs from CPNs is pH‐dependent such that significantly faster drug release at mildly acidic pH of 5.0 compared with physiological pH 7.4 is observed. Time and dose‐dependent in vitro cytotoxicity tests of blank and CPT‐loaded nanoparticles are performed by real‐time cell electronic sensing (RT‐CES) assay with hepatocellular carcinoma cells (Huh7). The results indicate that CPNs can be effectively utilized as vehicles for pH‐triggered release of anticancer drugs. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 114–122     

Popcorn‐Shaped Magnetic Core–Plasmonic Shell Multifunctional Nanoparticles for the Targeted Magnetic Separation and Enrichment,Label‐Free SERS Imaging,and Photothermal Destruction of Multidrug‐Resistant Bacteria

Over the last few years, one of the most important and complex problems facing our society is treating infectious diseases caused by multidrug‐resistant bacteria (MDRB), by using current market‐existing antibiotics. Driven by this need, we report for the first time the development of the multifunctional popcorn‐shaped iron magnetic core–gold plasmonic shell nanotechnology‐driven approach for targeted magnetic separation and enrichment, label‐free surface‐enhanced Raman spectroscopy (SERS) detection, and the selective photothermal destruction of MDR Salmonella DT104. Due to the presence of the “lightning‐rod effect”, the core–shell popcorn‐shaped gold‐nanoparticle tips provided a huge field of SERS enhancement. The experimental data show that the M3038 antibody‐conjugated nanoparticles can be used for targeted separation and SERS imaging of MDR Salmonella DT104. A targeted photothermal‐lysis experiment, by using 670 nm light at 1.5 W cm^?2 for 10 min, results in selective and irreparable cellular‐damage to MDR Salmonella. We discuss the possible mechanism and operating principle for the targeted separation, label‐free SERS imaging, and photothermal destruction of MDRB by using the popcorn‐shaped magnetic/plasmonic nanotechnology.     

Topotecan‐Loaded Mesoporous Silica Nanoparticles for Reversing Multi‐Drug Resistance by Synergetic Chemoradiotherapy

Multi‐drug resistance (MDR) has become a major challenge for the further improvement of chemotherapy. Thus, more effective strategies for further enhancing the treatment against cancer by overcoming MDR are warranted. In this study, by the encapsulation of the radiosensitizing drug TPT into mesoporous silica nanoparticles (MSNs), the combined use of drug‐delivered chemotherapy and high‐energy X‐ray induced radiotherapy could produce synergetic chemoradiotherapeutic effects to kill multi‐drug resistant cells through significant DNA damage, thus leading to an efficient circumvention of MDR. We hope that this synergetic dual‐mode treatment strategy may achieve higher oncolytic efficacy and find use in future clinical anti‐MDR applications.     

Poly[lactic‐co‐(glycolic acid)]‐Grafted Hyaluronic Acid Copolymer Micelle Nanoparticles for Target‐Specific Delivery of Doxorubicin

PLGA‐grafted HA copolymers were synthesized and utilized as target specific micelle carriers for DOX. For grafting hydrophobic PLGA chains onto the backbone of hydrophilic HA, HA was solubilized in an anhydrous DMSO by nano‐complexing with dimethoxy‐PEG. The carboxylic groups of HA were chemically grafted with PLGA, producing HA‐g‐PLGA copolymers. Resultant HA‐g‐PLGA self‐assembled in aqueous solution to form multi‐cored micellar aggregates and DOX was encapsulated during the self‐assembly. DOX‐loaded HA‐g‐PLGA micelle nanoparticles exhibited higher cellular uptake and greater cytotoxicity than free DOX for HCT‐116 cells that over‐expressed HA receptor, suggesting that they were taken up by the cells via HA receptor‐mediated endocytosis.

     

Near‐Infrared Light‐Mediated Photoactivation of a Platinum Antitumor Prodrug and Simultaneous Cellular Apoptosis Imaging by Upconversion‐Luminescent Nanoparticles

Platinum‐based drugs are among the most active antitumor reagents in clinical practice; their application is limited by side effects and drug resistance. A novel and personalized near‐infrared (NIR) light‐activated nanoplatform is obtained by combining a photoactivatable platinum(IV) prodrug and a caspase imaging peptide conjugated with silica‐coated upconversion‐luminescent nanoparticles (UCNPs) for the remote control of antitumor platinum prodrug activation, and simultaneously for real‐time imaging of apoptosis induced by activated cytotoxicity. Upon NIR light illumination, the Pt^IV prodrug complex is activated at the surface of the nanoparticle and active components are selectively released which display cytotoxicity against human ovarian carcinoma A2780 cells and its cisplatin‐resistant variant A2780cis cells. More importantly, the caspases enzymes triggered by cytotoxicity would effectively cleave the probe peptide, thereby allowing the direct imaging of apoptosis in living cells.     

Co‐Delivery of Docetaxel and p44/42 MAPK siRNA Using PSMA Antibody‐Conjugated BSA‐PEI Layer‐by‐Layer Nanoparticles for Prostate Cancer Target Therapy

How to overcome the low accumulation of chemotherapeutic agent in tumor tissue and exhibit multitherapeutics remains an ongoing challenge for cancer treatment. Here, a simple method is demonstrated that used to prepare prostate‐specific membrane antigen antibody (PSMA_ab)‐conjugated fluorescent bovine serum albumin (BSA)‐branched polyethylenimine layer‐by‐layer nanoparticles (BSA‐PEI_LBL NPs) for co‐delivery of docetaxel (DTX) and p44/42 mitogen‐activated protein kinase (MAPK) small interfering RNA (p44/42 MAPK siRNA) as synergistic and selective inhibition of cancer cell proliferation platform. The results show the levels of α‐tubulin and p44/42 MAPK in CWR22R cells are significantly reduced after treatment with PSMA_ab‐conjugated DTX/BSA‐PEI_LBL/siRNA NPs. Consequently, the 50% cellular growth inhibition (IC₅₀) values of the NPs loaded with both DTX and p44/42 MAPK siRNA are ≈2.1‐fold less than those for the NPs only loaded with DTX. The median survival significantly prolongs from 18 d to upward 45 d compared to mice that receive same dose (12 mg kg⁻¹) of free DTX. The results suggest this synergistic delivery system may be a promising clinical treatment in prostate cancer.

     

Self‐Assembled Aptamer‐Based Drug Carriers for Bispecific Cytotoxicity to Cancer Cells

Monovalent aptamers can deliver drugs to target cells by specific recognition. However, different cancer subtypes are distinguished by heterogeneous biomarkers and one single aptamer is unable to recognize all clinical samples from different patients with even the same type of cancers. To address heterogeneity among cancer subtypes for targeted drug delivery, as a model, we developed a drug carrier with a broader recognition range of cancer subtypes. This carrier, sgc8c‐sgd5a (SD), was self‐assembled from two modified monovalent aptamers. It showed bispecific recognition abilities to target cells in cell mixtures; thus broadening the recognition capabilities of its parent aptamers. The self‐assembly of SD simultaneously formed multiple drug loading sites for the anticancer drug doxorubicin (Dox). The Dox‐loaded SD (SD–Dox) also showed bispecific abilities for target cell binding and drug delivery. Most importantly, SD–Dox induced bispecific cytotoxicity in target cells in cell mixtures. Therefore, by broadening the otherwise limited recognition capabilities of monovalent aptamers, bispecific aptamer‐based drug carriers would facilitate aptamer applications for clinically heterogeneous cancer subtypes that respond to the same cancer therapy.     

Study of Intracellular Delivery of Doxorubicin from Poly(lactide‐co‐glycolide) Nanoparticles by Means of Fluorescence Lifetime Imaging and Confocal Raman Microscopy

The intracellular delivery of Doxorubicin (Dox) from poly(lactide‐co‐glycolide) (PLGA) nanoparticles stabilised with bovine serum albumin, in HepG2 cells, is studied via flow cytometry, fluorescence lifetime imaging microscopy (FLIM), confocal Raman microscopy (CRM) and cell viability studies. Flow cytometry shows that the initial uptake of PLGA and Dox follow the same kinetics. However, following 8 h of incubation, the fluorescence intensity and cellular uptake of Dox decreases, while in the case of PLGA both parameters remain constant. FLIM shows the presence of a single‐lifetime species, with a lifetime of 1.15 ns when measured inside the cells. Cell viability decreases by approximately 20% when incubated for 24 h with PLGA loaded with Dox, with a particle concentration of 100 µg · mL^?1. At the single‐cell level, CRM shows changes in the bands from DNA and proteins in the cell nucleus when incubated with PLGA loaded with Dox.