Tyrosinase (TYR) is an important biomarker of melanoma. The exploration of fluorescent pr-obes-based composites is beneficial to build an integrative platform for the diagnosis and treatment of melanoma. Herein, a multifunctional nanocomposite IOBOH@BSA activated by TYR is developed for selective imaging and ablation of melanoma. The chemical structure of IOBOH enables the fluorescence (FL) imaging activated by TYR, photoacoustic (PA) imaging, and photodynamic-photothermal activity by regulating the balance between radiative decay and non-radiative decay. IOBOH combined with bovine serum albumin (IOBOH@BSA) presents the response to TYR and realizes FL imaging with mitochondria-targeting in melanoma. Moreover, IOBOH@BSA shows excellent photothermal ability and is applied for PA imaging. After IOBOH@BSA is activated by TYR, the singlet oxygen generation increases obviously. IOBOH@BSA can realize TYR-activated imaging and photodynamic-photothermal therapy of melanoma. The development of TYR-activated multifunctional nanocomposites promotes the precise imaging and improves the therapeutic effect of melanoma.

Tumor microenvironment (TME) plays an important role in tumor progression, metastasis and therapy resistance. Remodeling the TME has recently been deemed an attractive tumor therapeutic strategy. Due to its complexity and heterogeneity, remodeling the TME still faces great challenges. With the great advantage of drug loading ability, tumor accumulation, multifactor controllability, and persistent guest molecule release ability, mesoporous nanodrug delivery systems (MNDDSs) have been widely used as effective antitumor drug delivery tools as well as remolding TME. This review summarizes the components and characteristics of the TME, as well as the crosstalk between the TME and cancer cells and focuses on the important role of drug delivery strategies based on MNDDSs in targeted remodeling TME metabolic and synergistic anticancer therapy.

A triple stimuli-responsive drug delivery platform involving doxorubicin, 5-fluoro-2-deoxy uridine and folic acid was fabricated on mesoporous silica nanoparticles for targeting delivery against a highly aggressive murine lymphoma called Dalton's lymphoma. Fabrication of the unique construct by amalgamating active and passive targeting mechanisms offers a novel hyper-chimeric platform for a stimuli-responsive drug delivery system. The novel construct enables efficient and precise delivery of the precious cargo to the tumor sites. Active targeting by folic acid directs the doxorubicin and 5-fluoro-2-deoxy uridine in the close proximities of the tumor cells, causing efficient killing and significant growth inhibition. Isobologram models, zero interaction potency dose-response surface plots and matrices were generated to evaluate the combination synergism of the two drugs. Therapy with the dual drug-bearing construct in mice with established tumors significantly reduced the tumor load and enhanced the survival of the animals compared with the untreated control. Therapy with the dual delivery system also augmented the innate and adaptive immune defense mechanisms of the treated animals. CD8⁺ T cells, natural killer cells and the dendritic cells from the treated group following successful therapy with the novel construct showed enhanced cytotoxicity and growth inhibitory capacities against DL tumor cells.

Mesoporous silica nanoparticles (MSNs) displays interesting properties for biomedical applications such as high chemical stability, large surface area and tunable pores diameters and volumes, allowing the incorporation of large amounts of drugs, protecting them from deactivation and degradation processes acting as an excellent nanoplatform for drug delivery. However, the functional MSNs do not present the ability to transport the therapeutics without any leakage until reach the targeted cells causing side effects. On the other hand, the hydroxyls groups available on MSNs surface allows the conjugation of specific molecules which can binds to the overexpressed Enhanced Growth Factor Receptor (EGFR) in many tumors, representing a potential strategy for the cancer treatment. Beyond that, the targeting molecules conjugate onto mesoporous surface increase its cell internalization and act as gatekeepers blocking the mesopores controlling the drug release. In this context, multifunctional MSNs emerge as stimuli-responsive controlled drug delivery systems (CDDS) to overcome drawbacks as low internalization, premature release before to reach the region of interest, several side effects and low effectiveness of the current treatments. This review presents an overview of MSNs fabrication methods and its properties that affects drug delivery as well as stimuli-responsive CDDS for cancer treatment.

Staphylococcus aureus ( S. aureus) is a causative agent in life-threatening human diseases that afflict millions of people annually. Traditional antibiotic treatments are becoming less efficient because S. aureus can invade host cells including osteoblasts and macrophages, constituting a reservoir that is relatively protected from antibiotics that can lead to recrudescent infection. We herein report a unique intracellular antibiotic delivery nanoparticle, which is composed of (i) a mesoporous silica nanoparticle (MSN) core loaded with gentamicin, (ii) an infected microenvironment (bacterial toxin)-responsive lipid bilayer surface shell, and (iii) bacteria-targeting peptide ubiquicidin (UBI_29-41) that is immobilized on the lipid bilayer surface shell. The lipid material acts as a gate that prevents drug release before the MSNs reach the target cells or tissue, at which point they are degraded by bacterial toxins to rapidly release the drug, thus eliminating efficient bacteria. We confirm rapid drug release in the presence of bacteria in an extracellular model and observe that S. aureus growth is effectively inhibited both in vitro and in vivo of planktonic and intracellular infection. The inflammation-related gene expression in infected preosteoblast or macrophage is also downregulated significantly after treatment by the antibiotic delivery nanoparticles. The antibiotic delivery nanoparticles offer advantages in fighting intracellular pathogens and eliminating the inflammation caused by intracellular bacterial infections.

The present review analyzes various approaches for the design and synthesis of different nanoparticles for imaging and therapy. Nanoparticles for computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET) and optical imaging are discussed. The influence of nanoparticle size, shape, surface charge, composition, surface functionalization, active targeting and other factors on imaging and therapeutic efficacy is analyzed. Cyto- and genotoxicity of nanoparticles are also discussed. Special attention in the review is paid to the imaging of apoptotic tissues and cells in different diseases.

The cell interior is a crowded chemical space, which limits the diffusion of molecules and organelles within the cytoplasm, affecting the rates of chemical reactions. We provide insight into the relationship between non-specific intracellular diffusion and cytoskeletal integrity. Quantum dots entered the cell through microinjection and their spatial coordinates were captured by tracking their fluorescence signature as they diffused within the cell cytoplasm. Particle tracking revealed significant enhancement in the mobility of biocompatible quantum dots within fibrosarcoma cells versus their healthy counterparts, fibroblasts, as well as in actin destabilized fibroblasts versus untreated fibroblasts. Analyzing the displacement distributions provided insight into how the heterogeneity of the cell cytoskeleton influences intracellular particle diffusion. We demonstrate that intracellular diffusion of non-specific nanoparticles is enhanced by disrupting the actin network, which has implications for drug delivery efficacy and trafficking.

Hypermethylated cancer populations are hard to treat due to their enhanced chemo-resistance, characterized by aberrant methylated DNA subunits. Herein, we report on invoking response from such a cancer lineage to chemotherapy utilizing multifunctional copper telluride (Cu2-XTe) nanocubes (NCs) as photothermal and photodynamic agents, leading to significant anticancer activity. The NCs additionally possessed photoacoustic and X-ray contrast imaging abilities that could serve in image-guided therapeutic studies.

A simple, crude Jatropha curcas (JC) oil-based synthesis approach, devoid of any toxic phosphine and pyrophoric ligands, to produce size and shape tuned CdSe QDs and a further copper sulfide (Cu2S) encasing is presented. The QDs exhibited excellent photoluminescent properties with narrow band gap emission. Furthermore, the Cu2S shell rendered additional cytocompatibility and stability to the hybrid nanomaterial, which are major factors for translational and clinical applications of QDs. The nanocomposites were PEGylated and folate conjugated to augment their cytoamiability and enhance their specificity towards cancer cells. The nanohybrids possess potentials for visible, near infrared (NIR), photoacoustic (PA) and computed tomography (μCT) imaging. The diverse functionality of the composite was derived from the multi-channel imaging abilities and thermal competence on NIR laser irradiation to specifically actuate the photo-thermal ablation of brain cancer cells.

Extensive cancer research in the past few decades has identified the existence of a rare subpopulation of stem cells in the grove of cancer cells. These cells are known as the cancer stem cells marked by the presence of surface biomarkers, multi-drug resistance pumps and deregulated self-renewal pathways (SRPs). They have a crucial role in provoking cancer cells leading to tumorigenesis and its progressive metastasis. Cancer stem cells (CSCs) are much alike to normal stem cells in their self-renewal mechanisms. However, deregulations in the SRPs are seen in CSCs, making them resistant to conventional chemotherapeutic agents resulting in the tumor recurrence. Current treatment strategies in cancer fail to detect and differentiate the CSCs from their non-tumorigenic progenies owing to absence of specific biomarkers. Now, it has become imperative to understand complex functional biology of CSCs, especially the signaling pathways to design improved treatment strategies to target them. It is hopeful that the SRPs in CSCs offer a promising target to alter their survival strategies and impede their tumorigenic potential. However, there are many perils associated with the direct targeting method by conventional therapeutic agents such as off targets, poor bioavailability and poor cellular distribution. Recent evidences have shown an increased use of small molecule antagonists directly to target these SRPs may lead to severe side-effects. An alternative to solve these issues could be an appropriate nanoformulation. Nanoformulations of these molecules could provide an added advantage for the selective targeting of the pathways especially Hedgehog, Wnt, Notch and B-cell-specific moloney murine leukemia virus integration site 1 in the CSCs while sparing the normal stem cells. Hence, to achieve this goal a complete understanding of the molecular pathways corroborate with the use of holistic nanosystem (nanomaterial inhibition molecule) could possibly be an encouraging direction for future cancer therapy.

The in vitro and in vivo uptake, toxicological analysis and anti-angiogenic theranostic prospect of FITC loaded (FITC-Si) and suramin loaded (Sur-Si) silica nanoparticles are presented. FITC/suramin encapsulated silica nanoparticles (NPs) with an average size of <30 nm were synthesized. The uptake of FITC-Si by human umbilical vein endothelial cells (HuVECs) (in vitro) and by early stage medaka embryos (in vivo) was monitored by fluorescence microscopy. The nanoformulation was found to be biocompatible with both cells and embryos. The cytotoxicity analysis, tubulogenesis and migration assay confirmed the anti-angiogenic potential of Sur-Si NPs in HuVECs. The imaging of medaka embryos exposed to FITC-Si, their survival and hatching rate and biocompatibility post FITC-Si exposure were documented. The in vivo drug delivery mediated anti-angiogenic potential of Sur-Si NPs was assessed by survival and hatching rate analysis along with morphological indicators. At higher concentrations, Sur-Si proved lethal to embryos, whereas at lower concentrations it was rather an efficient anti-angiogenic formulation leading to malformed vasculogenesis and inhibited intersegmental vessel formation in an efficient dose dependent mode. The results indicate the potential application of such nanoformulation in future anti-angiogenic theranostics.

Combination therapy for cancer patients is an important standard of care protocol because it can elicit synergistic therapeutic effects and reduce systemic toxicity by simultaneously modulating multiple cell-signaling pathways and overcoming multidrug resistance. Nanocarriers are expected to play a major role in delivering multiple drugs to tumor tissues by overcoming biological barriers. However, especially considering the different physical chemistry of chemotherapeutic drugs, it is highly desirable to develop a codelivery nanocarrier for controlled and targeted delivery of both hydrophobic and hydrophilic drugs. This review reports the recent developments in various combinational drug delivery systems and the simultaneous use of combinational drug delivery systems with functional agents.

Novel targeting agents against neuroblastoma based on the meta-iodobenzylguanidine (MIBG) moiety were synthesized and biologically evaluated for nanocarrier vectorization. These compounds have been anchored on the surface of drug loaded mesoporous silica nanocarriers, resulting in the improved cellular uptake in tumoral cells. Neuroblastoma (NB) is the most frequent extracranial pediatric tumor. Advanced forms of the disease (metastatic and/or refractory) have a dismal prognosis despite the combination of chemotherapy, radiotherapy, surgery and bone narrow transplants. These treatments carry severe side effects and, in some cases, compromise the life of the patient. MIBG has been widely applied in the medical diagnosis of NB due to its affinity for tumor cells through the norepinephrine transporter (NET), which is expressed in 90% of NB tumors. The exclusive accumulation of MIBG in neuroblastoma has been widely studied; however, its properties have been never exploited as a targeting agent in nanocarrier drug delivery systems. Several structural analogues of MIBG have been prepared and attached on the surface of nanocarriers. Their selective internalization has been tested against human neuroblastoma cells, which show, in the best case, cellular uptake four times higher than that of the naked nanosystem. Furthermore, in vivo experiments showed preferential and selective accumulation and retention of the targeted nanosystem comparing with the naked and only PEGylated counterpart systems. This novel nanosystem could be easily applicable to all kinds of drug delivery nanocarriers, providing a universal tool for neuroblastoma chemotherapies that is superior to classical approaches through a novel nanosystem exclusively designed to target this terrible malignancy.

A size and shape tuned, multifunctional metal chalcogenide, Cu2S-based nanotheranostic agent is developed for trimodal imaging and multimodal therapeutics against brain cancer cells. This theranostic agent was highly efficient in optical, photoacoustic and X-ray contrast imaging systems. The folate targeted NIR-responsive photothermal ablation in synergism with the chemotherapeutic action of doxorubicin proved to be a rapid precision guided cancer-killing module. The multi-stimuli, i.e., pH-, thermo- and photo-responsive drug release behavior of the nanoconjugates opens up a wider corridor for on-demand triggered drug administration. The simple synthesis protocol, combined with the multitudes of interesting features packed into a single nanoformulation, clearly demonstrates the competing role of this Cu2S nanosystem in future cancer treatment strategies.

To minimize cardiotoxicity and to increase the bioavailability of doxorubicin, polymersomes based on redox sensitive amphiphilic triblock copolymer poly(polyethylene glycol methacrylate)-poly(caprolactone)-s-s-poly(caprolactone)-poly(polyethylene glycol methacrylate) (pPEGMA-PCL-ss-PCL-pPEGMA) with disulfide linkage were designed and developed. The polymers were synthesized by ring opening polymerization (ROP) of ε-caprolactone followed by atom transfer radical polymerization (ATRP) of PEGMA. The triblock copolymers demonstrated various types of nanoparticle morphologies by varying hydrophobic/hydrophilic content of polymer blocks, with PEGMA content of ∼18% in the triblock copolymer leading to the formation of polymersomes in the size range ∼150 nm. High doxorubicin loading content of ∼21% was achieved in the polymersomes. Disulfide linkages were incorporated in the polymeric backbone to facilitate degradation of the nanoparticles by the intracellular tripeptide glutathione (GSH), leading to intracellular drug release. Release studies showed ∼59% drug release in pH 5.5 in the presence of 10 mM GSH, whereas only ∼19% was released in pH 7.4. In cellular uptake studies, dual targeted polymersomes showed ∼22-fold increase in cellular uptake efficiency in breast cancer cell lines (BT474 and MCF-7) as compared to nontargeted polymersomes with higher apoptosis rates. In vivo studies on Ehrlich's ascites tumor (EAT) bearing Swiss albino mouse model showed ∼85% tumor regression as compared to free doxorubicin (∼42%) without any significant cardiotoxicity associated with doxorubicin. The results indicate enhanced antitumor efficacy of the redox sensitive biocompatible nanosystem and shows promise as a potential drug nanocarrier in cancer therapeutics.

Methoxy PEGylated nanoparticles (mPEG-NPs) are increasingly used for cancer imaging and therapy. Here we describe a general and simple approach to confer tumor tropism to any mPEG-NP. We demonstrate this approach with humanized bispecific antibodies (BsAbs) that can bind to both mPEG molecules on mPEG-NPs and to EGFR or HER2 molecules overexpressed on the surface of cancer cells. Simple mixing of BsAbs with mPEG-NPs can mediate preferential binding of diverse mPEG-NPs to cancer cells that overexpress EGFR or HER2 under physiological conditions and significantly increase cancer cell killing by liposomal doxorubicin to EGFR(+) and HER2(+) cancer cells. BsAbs modification also enhanced accumulation of fluorescence-labeled NPs and significantly increased the anticancer activity of drug-loaded NPs to antigen-positive human tumors in a mouse model. Anti-mPEG BsAbs offer a simple one-step method to confer tumor specificity to mPEG-NPs for enhanced tumor accumulation and improved therapeutic efficacy.

To develop carriers for efficient anti-cancer drug delivery with reduced side effects, a biocompatible and redox-responsive nanocontainer based on mesoporous silica nanoparticles (MSNs) for tumor-targeted triplex therapy was reported in this study. The nanocontainer was fabricated by immobilizing cytochrome c (CytC) onto the MSNs as sealing agent via intermediate linkers of disulfide bonds for redox-responsive intracellular drug delivery. AS1411 aptamer was further tailored onto MSNs for cell/tumor targeting. The successful construction of redox- responsive MSNs was confirmed by BET/BJH analysis, transmission electron microscopy, Fourier transform infrared spectroscopy, fluorescence spectroscopy and thermogravimetric analysis (TGA), respectively. Detailed investigations demonstrated that anticancer drug of doxorubicin (DOX) loaded nanocontainer could be triggered by reductant (e.g. glutathione) within cellular microenvironment and release DOX to induce tumor cell apoptosis in vitro. More importantly, the nanocontainer displayed great potential for tumor targeting and achieved triplex therapy effects on the tumor inhibition in vivo through the loading DOX, gatekeeper of CytC and AS1411 aptamer, which were reflected by the change of tumor size, TUNEL staining and HE staining assays.

Designing of drug nanocarriers to aid delivery of therapeutics is an expanding field that can improve medical treatments. Nanocarriers are often functionalized with elements that recognize cell-surface molecules involved in subcellular transport to improve targeting and endocytosis of therapeutics. Combination-targeting using several affinity elements further modulates this outcome. The most studied example is endothelial targeting via multiple cell adhesion molecules (CAMs), which mimics the strategy of leukocytes to adhere and traverse the vascular endothelium. Yet, the implications of this strategy on intracellular transport and in vivo biodistribution remain uncharacterized. We examined this using nanocarriers functionalized for dual- or triple-targeting to intercellular, platelet-endothelial, and/or vascular CAMs (ICAM-1, PECAM-1, VCAM-1). These molecules differ in expression level, location, pathological stimulation, and/or endocytic pathway. In endothelial cells, binding of PECAM-1/VCAM-1-targeted nanocarriers was intermediate to single-targeted counterparts and enhanced in disease-like conditions. ICAM-1/PECAM-1-targeted nanocarriers surpassed PECAM-1/VCAM-1 in control, but showed lower selectivity toward disease-like conditions. Triple-targeting resulted in binding similar to ICAM-1/PECAM-1 combination and displayed the highest selectivity in disease-like conditions. All combinations were effectively internalized by the cells, with slightly better performance when targeting receptors of different endocytic pathways. In vivo, ICAM-1/PECAM-1-targeted nanocarriers outperformed PECAM-1/VCAM-1 in control and disease-like conditions, and triple-targeted counterparts slightly enhanced this outcome in some organs. As a result, delivery of a model therapeutic cargo (acid sphingomyelinase, deficient in Niemann-Pick disease A-B) was enhanced to all affected organs by triple-targeted nanocarriers, particularly in disease-like conditions. Therefore, multi-CAM targeting may aid the optimization of some therapeutic nanocarriers, where the combination and multiplicity of the affinity moieties utilized allow modulation of targeting performance.

Nonspecificity and cardiotoxicity are the primary limitations of current doxorubicin chemotherapy. To minimize side effects and to enhance bioavailability of doxorubicin to cancer cells, a dual-targeted pH-sensitive biocompatible polymeric nanosystem was designed and developed. An ATRP-based biodegradable triblock copolymer, poly(poly(ethylene glycol) methacrylate)-poly(caprolactone)-poly(poly(ethylene glycol) methacrylate) (pPEGMA-PCL-pPEGMA), conjugated with doxorubicin via an acid-labile hydrazone bond was synthesized and characterized. Dual targeting was achieved by attaching folic acid and the AS1411 aptamer through EDC-NHS coupling. Nanoparticles of the functionalized triblock copolymer were prepared using the nanoprecipitation method, resulting in an average particle size of ∼140 nm. The biocompatibility of the nanoparticles was evaluated using MTT cytotoxicity assays, blood compatibility studies, and protein adsorption studies. In vitro drug release studies showed a higher cumulative doxorubicin release at pH 5.0 (∼70%) compared to pH 7.4 (∼25%) owing to the presence of the acid-sensitive hydrazone linkage. Dual targeting with folate and the AS1411 aptamer increased the cancer-targeting efficiency of the nanoparticles, resulting in enhanced cellular uptake (10- and 100-fold increase in uptake compared to single-targeted NPs and non-targeted NPs, respectively) and a higher payload of doxorubicin in epithelial cancer cell lines (MCF-7 and PANC-1), with subsequent higher apoptosis, whereas a normal (noncancerous) cell line (L929) was spared from the adverse effects of doxorubicin. The results indicate that the dual-targeted pH-sensitive biocompatible polymeric nanosystem can act as a potential drug delivery vehicle against various epithelial cancers such as those of the breast, ovary, pancreas, lung, and others.

We report here that the surface topography of colloidal mesoporous silica nanoparticles (MSNs) plays a key role on their bionano-interactions by driving the adsorption of biomolecules on the nanoparticle through a matching mechanism between the surface cavities characteristics and the biomolecules stereochemistry. This conclusion was drawn by analyzing the biophysicochemical properties of colloidal MSNs in the presence of single biomolecules, such as alginate or bovine serum albumin (BSA), as well as dispersed in a complex biofluid, such as human blood plasma. When dispersed in phosphate buffered saline media containing alginate or BSA, monodisperse spherical MSNs interact with linear biopolymers such as alginate and with a globular protein such as bovine serum albumin (BSA) independently of the surface charge sign (i.e. positive or negative), thus leading to a decrease in the surface energy and to the colloidal stabilization of these nanoparticles. In contrast, silica nanoparticles with irregular surface topographies are not colloidally stabilized in the presence of alginate but they are electrosterically stabilized by BSA through a sorption mechanism that implies reversible conformation changes of the protein, as evidenced by circular dichroism (CD). The match between the biomolecule size and stereochemistry with the nanoparticle surface cavities characteristics reflects on the nanoparticle surface area that is accessible for each biomolecule to interact and stabilize any non-rigid nanoparticles. On the other hand, in contact with variety of biomolecules such as those present in blood plasma (55%), MSNs are colloidally stabilized regardless of the topography and surface charge, although the identity of the protein corona responsible for this stabilization is influenced by the surface topography and surface charge. Therefore, the biofluid in which nanoparticles are introduced plays an important role on their physicochemical behavior synergistically with their inherent characteristics (e.g., surface topography).

Although there are several studies reporting the promising biological efficiency of mesoporous silica nanoparticles (loaded with antitumoral drugs) against cancer cells and tumors, there are no reports on the influence of the bio-nano interface interactions on the molecular diffusion process occurring along their pores. In this context, we show here that the protein coating formed on multifunctionalized colloidal mesoporous silica nanoparticles (MSNs) dispersed in a cell culture medium decreases the release of camptothecin (CPT, a hydrophobic antitumoral drug) from the pores of MSNs. This effect is related to the adsorption of biomolecules on the nanoparticle surface, which partially blocks the pores. Parallely, the hydrophobic functionalization inside the pores can offer suitable sites for the adsorption of other molecules present in the cell culture medium depending on the hydrophobicity, size, and conformation aspects of these molecules and adsorption sites of MSNs. Thus, the molecular cargo loaded in the pores (i.e. CPT) can be replaced by specific molecules present in the dispersion medium. As a consequence, we show that a non-permeable cellular staining molecule such as SYTOX green can be incorporated in MSNs through this mechanism and internalized by cells in an artificial fashion. By extrapolating this phenomenon for applications in vivo, one has to consider now the possible manifestation of unpredicted biological effects from the use of porous silica nanoparticles and others with similar structure due to these internalization aspects.

The photothermal effect of single-walled carbon nanotubes (SWCNTs) in combination with the anticancer drug doxorubicin (DOX) for targeting and accelerated destruction of breast cancer cells is demonstrated in this paper. A targeted drug-delivery system was developed for selective killing of breast cancer cells with polyethylene glycol biofunctionalized and DOX-loaded SWCNTs conjugated with folic acid. In our work, in vitro drug-release studies showed that the drug (DOX) binds at physiological pH (pH 7.4) and is released only at a lower pH, ie, lysosomal pH (pH 4.0), which is the characteristic pH of the tumor environment. A sustained release of DOX from the SWCNTs was observed for a period of 3 days. SWCNTs have strong optical absorbance in the near-infrared (NIR) region. In this special spectral window, biological systems are highly transparent. Our study reports that under laser irradiation at 800 nm, SWCNTs exhibited strong light-heat transfer characteristics. These optical properties of SWCNTs open the way for selective photothermal ablation in cancer therapy. It was also observed that internalization and uptake of folate-conjugated NTs into cancer cells was achieved by a receptor-mediated endocytosis mechanism. Results of the in vitro experiments show that laser was effective in destroying the cancer cells, while sparing the normal cells. When the above laser effect was combined with DOX-conjugated SWCNTs, we found enhanced and accelerated killing of breast cancer cells. Thus, this nanodrug-delivery system, consisting of laser, drug, and SWCNTs, looks to be a promising selective modality with high treatment efficacy and low side effects for cancer therapy.