Folate-targeting magnetic core-shell nanocarriers for selective drug release and imaging

One of the most urgent medical requirements for cancer diagnosis and treatment is how to construct a multifunctional vesicle for simultaneous diagnostic imaging and therapeutic applications. In our study, superparamagnetic iron oxide nanocrystals (SPIONs) and doxorubicin hydrochloride (DOX) are co-encapsulated into PLGA/polymeric liposome core-shell nanocarriers for achieving simultaneous magnetic resonance imaging and targeting drug delivery. The core-shell nanocarrier was self-assembled from a hydrophobic PLGA core and a hydrophilic folate coated PEGlated lipid shell. The experiment showed that folate-targeting magnetic core-shell nanocarriers show clear core-shell structure, excellent magnetism and controlled drug release behavior. Importantly, the core-shell nanoparticles achieve the possibility of co-delivering drugs and SPIONs to the same cells for enhancing magnetic resonance imaging (MRI) effect and improving drug delivery efficiency simultaneously. Our data suggests that the folate-targeting magnetic core-shell nanocarriers (FMNs) could provide effective cancer-targeting and MRI as well as drug delivery. The FMNs may become a useful nanomedical carrier system for cancer diagnosis and treatment.     

Real-time SERS monitoring anticancer drug release along with SERS/MR imaging for pH-sensitive chemo-phototherapy

In situ and real-time monitoring of responsive drug release is critical for the assessment of pharmacodynamics in chemotherapy. In this study, a novel pH-responsive nanosystem is proposed for real-time monitoring of drug release and chemo-phototherapy by surface-enhanced Raman spectroscopy (SERS). The Fe₃O₄@Au@Ag nanoparticles (NPs) deposited graphene oxide (GO) nanocomposites with a high SERS activity and stability are synthesized and labeled with a Raman reporter 4-mercaptophenylboronic acid (4-MPBA) to form SERS probes (GO-Fe₃O₄@Au@Ag-MPBA). Furthermore, doxorubicin (DOX) is attached to SERS probes through a pH-responsive linker boronic ester (GO-Fe₃O₄@Au@Ag-MPBA-DOX), accompanying the 4-MPBA signal change in SERS. After the entry into tumor, the breakage of boronic ester in the acidic environment gives rise to the release of DOX and the recovery of 4-MPBA SERS signal. Thus, the DOX dynamic release can be monitored by the real-time changes of 4-MPBA SERS spectra. Additionally, the strong T₂ magnetic resonance (MR) signal and NIR photothermal transduction efficiency of the nanocomposites make it available for MR imaging and photothermal therapy (PTT). Altogether, this GO-Fe₃O₄@Au@Ag-MPBA-DOX can simultaneously fulfill the synergistic combination of cancer cell targeting, pH-sensitive drug release, SERS-traceable detection and MR imaging, endowing it great potential for SERS/MR imaging-guided efficient chemo-phototherapy on cancer treatment.     

Development of a novel thermal-sensitive multifunctional liposome with antibody conjugation to target EGFR-expressing tumors

A novel EGFR-targeting, thermal-sensitive multifunctional liposome (TSML) was developed based on manganese-doped magnetism-engineered iron oxide nanoparticles (MnMEIOs) and gold nanorods (AuNRs) for efficient photothermal therapy and magnetic resonance (MR) imaging. An Erbitux-conjugated TSML (Erb-TSML) was encapsulated with doxorubicin and gold nanorods conjugated with manganese-doped magnetism-engineered iron oxide nanoparticles, for theranostic applications of EGFR-positive tumors. The Erb-TSML selectively targeted EGFR-positive tumors and promoted tumor destruction by laser activation. Using confocal microscopy, MR and optical imaging, we demonstrated that Erb-TSML specifically bound to A431 tumor cells. No signs of major morphological damages to the normal tissues were observed in mice treated with Erb-TSML and laser, indicating this theranostic platform protected heart against doxorubicin-induced toxicity to normal tissues. These results indicate that the Erb-TSML may be a promising diagnostic and therapeutic platform for EGFR-overexpressing tumors.     

Theranostic tumor homing nanocarriers for the treatment of lung cancer

The drugs/strategies to selectively inhibit tumor blood supply have generated interest in recent years for enhancement of cancer therapeutics. The objective of this study was to formulate tumor homing PEGylated CREKA peptide conjugated theranostic nanoparticles of DIM-C-pPhC6H5 (DIM-P) and investigate in vivo antitumor activity as well as evaluate the targeted efficiency to lung tumors using imaging techniques. DIM-P loaded Nanoparticles (NCs-D) were prepared using lipids, and DOGS-NTA-Ni and the surface of NCs-D were modified with PEGylated CREKA peptide (PCNCs-D). PCNCs-D showed 3 fold higher binding to clotted plasma proteins in tumor vasculature compared to NCs-D. PCNCs-D showed 26% ± 4% and 22% ± 5% increase in tumor reduction compared to NCs-D in metastatic and orthotopic models respectively. In-vivo imaging studies showed ~ 40 folds higher migration of PCNCs-Di in tumor vasculature than NCs-Di. Our studies demonstrate the role of PCNCs-D as theranostic tumor homing drug delivery and imaging systems for lung cancer diagnosis and treatment.From the Clinical EditorThis study demonstrates a very efficient delivery system to address lung cancer growth through blood supply inhibition.     

Mesoporous silica-coated gold nanostars with drug payload for combined chemo-photothermal cancer therapy

Abstract

Combined chemo-photothermal therapy is attracting increasing attention in the treatment of cancers. In this work, PEGylated mesoporous SiO₂-coated gold nanostars (GNS@mSiO₂-PEG) were synthesised without using the cytotoxic surfactant cetyltrimethylammonium bromide as the template. Mesoporous nanostructures were obtained by poly(vinylpyrrolidone) protection of the outer silica shell and NaOH etching of the inner shell. GNS@mSiO₂-PEG exhibited good dispersity in medium and excellent photothermal effects. Loading capacity for the anticancer drug doxorubicin (DOX) was ～17.9%, and the drug release profile was pH- and light-responsive. In vitro studies revealed that the as-prepared nanocomposites featured good biocompatibility. Furthermore, the nanocomposites were readily internalised by cancer cells, and a combined chemo-photothermal therapy assay revealed that DOX-loaded GNS@mSiO₂-PEG have a higher therapeutic efficiency than individual therapies, demonstrating suitable synergistic effects.     

Transferrin targeted core-shell nanomedicine for combinatorial delivery of doxorubicin and sorafenib against hepatocellular carcinoma

Combinatorial drug delivery is an attractive, but challenging requirement of next generation cancer nanomedicines. Here, we report a transferrin-targeted core-shell nanomedicine formed by encapsulating two clinically used single-agent drugs, doxorubicin and sorafenib against liver cancer. Doxorubicin was loaded in poly(vinyl alcohol) nano-core and sorafenib in albumin nano-shell, both formed by a sequential freeze-thaw/coacervation method. While sorafenib from the nano-shell inhibited aberrant oncogenic signaling involved in cell proliferation, doxorubicin from the nano-core evoked DNA intercalation thereby killing > 75% of cancer cells. Upon targeting using transferrin ligands, the nanoparticles showed enhanced cellular uptake and synergistic cytotoxicity in ~ 92% of cells, particularly in iron-deficient microenvironment. Studies using 3D spheroids of liver tumor indicated efficient penetration of targeted core-shell nanoparticles throughout the tissue causing uniform cell killing. Thus, we show that rationally designed core-shell nanoparticles can effectively combine clinically relevant single-agent drugs for exerting synergistic activity against liver cancer.From the Clinical EditorTransferrin-targeted core-shell nanomedicine encapsulating doxorubicin and sorafenib was studied as a drug delivery system against hepatocellular carcinoma, resulting in enhanced and synergistic therapeutic effects, paving the way towards potential future clinical applications of similar techniques.     

Introduction of magnetic and supermagnetic nanoparticles in new approach of targeting drug delivery and cancer therapy application

Abstract

In this article, the recent applications of different types of magnetic nanoparticles such as α-Fe₂O₃ (hematite), γ-Fe₂O₃ (maghemite), Fe₃O₄ (magnetite), hexagonal (MFe₁₂O₁₉), garnet (M₃Fe₅O₁₂) and spinel (MFe₂O₄), where M represents one or more bivalent transition metals (Mn, Fe, Co, Ni, Ba, Sr, Cu, and Zn), and different materials for coating the surface of magnetic nanoparticles like poly lactic acid (PLA), doxorubicin hydrophobic (DOX-HCL), paclitaxel (PTX), EPPT-FITC, oleic acid, tannin, 3-Aminopropyltriethoxysilane (APTES), multi-wall carbon nanotubes (CNTs), polyethylenimine (PEI) and polyarabic acid in drug delivery, biomedicine and treatment of cancer, specially chemotherapy, are reviewed. MNPs possess large surface area to volume ratios because of their nano-size, low surface charge at physiological pH and they aggregate easily in solution due to their essential magnetic nature. These materials are widely used in biology and medicine in many cases. One targeted delivery technique that has gained prominence in recent years is the use of magnetic nanoparticles. In these systems, therapeutic compounds are attached to biocompatible magnetic nanoparticles and magnetic fields generated outside the body are focused on specific targets in vivo. The fields capture the particle complex, resulting in enhanced delivery to the target site. Also, the application of brand new supermagnetic nanoparticles, like Ba,SrFe₁₂O₁₉, is considered and studied in this paper.     

A smart O2-generating nanocarrier optimizes drug transportation comprehensively for chemotherapy improving

Drug transportation is impeded by various barriers in the hypoxic solid tumor, resulting in compromised anticancer efficacy. Herein, a solid lipid monostearin (MS)-coated CaO₂/MnO₂ nanocarrier was designed to optimize doxorubicin (DOX) transportation comprehensively for chemotherapy enhancement. The MS shell of nanoparticles could be destroyed selectively by highly-expressed lipase within cancer cells, exposing water-sensitive cores to release DOX and produce O₂. After the cancer cell death, the core-exposed nanoparticles could be further liberated and continue to react with water in the tumor extracellular matrix (ECM) and thoroughly release O₂ and DOX, which exhibited cytotoxicity to neighboring cells. Small DOX molecules could readily diffuse through ECM, in which the collagen deposition was decreased by O₂-mediated hypoxia-inducible factor-1 inhibition, leading to synergistically improved drug penetration. Concurrently, DOX-efflux-associated P-glycoprotein was also inhibited by O₂, prolonging drug retention in cancer cells. Overall, the DOX transporting processes from nanoparticles to deep tumor cells including drug release, penetration, and retention were optimized comprehensively, which significantly boosted antitumor benefits.     

Tumor-targeted Gd-doped mesoporous Fe3O4 nanoparticles for T1/T2 MR imaging guided synergistic cancer therapy

In this study, a novel intelligent nanoplatform to integrate multiple imaging and therapeutic functions for targeted cancer theranostics. The nanoplatform, DOX@Gd-MFe₃O₄ NPs, was constructed Gd-doped mesoporous Fe₃O₄ nanoparticles following with the doxorubicin (DOX) loading in the mesopores of the NPs. The DOX@Gd-MFe₃O₄ NPs exhibited good properties in colloidal dispersity, photothermal conversion, NIR triggered drug release, and high T₁/T₂ relaxicity rate (r₁=9.64 mM⁻¹s⁻¹, r₂= 177.71 mM⁻¹s⁻¹). Benefiting from the high MR contrast, DOX@Gd-MFe₃O₄ NPs enabled simultaneous T₁/T₂ dual-modal MR imagining on 4T1 bearing mice in vivo and the MR contrast effect was further strengthened by external magnetic field. In addition, the DOX@Gd-MFe₃O₄ NPs revealed the strongest inhibition to the growth of 4T1 in vitro and in vivo under NIR irradiation and guidance of external magnetic field. Moreover, biosafety was also validated by in vitro and in vivo tests. Thus, the prepared DOX@Gd-MFe₃O₄ NPs would provide a promising intelligent nanoplatform for dual-modal MR imagining guided synergistic therapy in cancer theranostics.     

Body distribution of SiO2–Fe3O4 core-shell nanoparticles after intravenous injection and intratracheal instillation

Nano-silicon dioxide (SiO₂) is used nowadays in several biomedical applications such as drug delivery and cancer therapy, and is produced on an industrial scale as additive to paints and coatings, cosmetics and food. Data regarding the long-term biokinetics of SiO₂ engineered nanoparticles (ENPs) is lacking. In this study, the whole-body biodistribution of SiO₂ core-shell ENPs containing a paramagnetic core of Fe₃O₄ was investigated after a single exposure via intravenous injection or intratracheal instillation in mice. The distribution and accumulation in different organs was evaluated for a period of 84 days using several techniques, including magnetic resonance imaging, inductively coupled plasma mass spectrometry, X-ray fluorescence and X-ray absorption near edge structure spectroscopy. We demonstrated that intravenously administered SiO₂ ENPs mainly accumulate in the liver, and are retained in this tissue for over 84 days. After intratracheal instillation, an almost complete particle clearance from the lung was seen after 84 days with distribution to spleen and kidney. Furthermore, we have strong evidence that the ENPs retain their original core-shell structure during the whole observation period. This work gives an insight into the whole-body biodistribution of SiO₂ ENPs and will provide guidance for further toxicity studies.     

Multimodal doxorubicin loaded magnetic nanoparticles for VEGF targeted theranostics of breast cancer

In presented paper we have developed new system for cancer theranostics based on vascular endothelial growth factor (VEGF) targeted magnetic nanoparticles. Conjugation of anti-VEGF antibodies with bovine serum albumin coated PEGylated magnetic nanoparticles allows for improved binding with murine breast adenocarcinoma 4T1 cell line and facilitates doxorubicin delivery to tumor cells. It was shown that intravenous injection of doxorubicin loaded VEGF targeted nanoparticles increases median survival rate of mice bearing 4T1 tumors up to 50%. On the other hand magnetic resonance imaging (MRI) of 4T1 tumors 24 h after intravenous injection showed accumulation of nanoparticles in tumors, thus allowing simultaneous cancer therapy and diagnostics.     

A theranostic nanocomposite system based on iron oxide-drug nanocages for targeted magnetic field responsive chemotherapy

In this work, a theranostic nanocage system was developed for the targeted delivery of the anti-cancer agents camptothecin (CPT) and luotonin A (LuA). The core of the nanocage system (Fe₃O₄@OA-AD-SP NCs) was formed by biogenically synthesized Fe₃O₄ nanoparticles (NPs) decorated with a model anti-cancer drug (AD) and biosurfactant saponin (SP). The Fe₃O₄@OA-AD-SP NCs showed a high lipophilic AD loading efficiency (>80%) and a controlled pH-responsive drug release in stimulated cancerous cells in pH 6.4 media buffer. In addition, Fe₃O₄@OA-AD-SP NCs exhibited better serum protein binding efficacy at physiological pH values (7.4), furthering the important role of SP surface decoration. Particularly, these NCs showed better chemotherapeutic efficacy when examined in MCF-7 and HeLa cancer cell lines with a specific targeting capacity. Therefore, this study provides a new nano platform based on magnetic targeting and pH responsive lipophilic anticancer drug delivery to the cancer site.     

Magnetic resonance and fluorescence imaging of doxorubicin-loaded nanoparticles using a novel in vivo model

We report here the in vivo combined-modality imaging of multifunctional drug delivery nanoparticles. These dextran core–based stealth liposomal nanoparticles (nanosomes) contained doxorubicin, iron oxide for magnetic resonance imaging (MRI) contrast, and BODIPY for fluorescence. The particles were long-lived in vivo because of surface decoration with polyethylene glycol and the incorporation of acetylated lipids that were ultraviolet cross-linked for physical stability. We developed a rodent dorsal skinfold window chamber that facilitated both MRI and non-invasive optical imaging of nanoparticle accumulation in the same tumors. Chamber tumors were genetically labeled with DsRed-2, which enabled co-localization of the MR images, the red fluorescence of the tumor, and the blue fluorescence of the nanoparticles. The nanoparticle design and MR imaging developed with the window chamber were then extended to orthotopic pancreatic tumors expressing DsRed-2. The tumors were MR-imaged using iron oxide–dextran liposomes and by fluorescence to demonstrate the deep imaging capability of these nanoparticles.From the Clinical EditorIn vivo combined-modality imaging of multifunctional drug delivery nanoparticles is discussed in this proof of principle paper.     

In vitro evaluation of novel polymer-coated magnetic nanoparticles for controlled drug delivery

Previously uncharacterized poly(N-isopropylacrylamide-acrylamide-allylamine)-coated magnetic nanoparticles (MNPs) were synthesized using silane-coated MNPs as a template for radical polymerization of N-isopropylacrylamide, acrylamide, and allylamine. Properties of these nanoparticles such as size, biocompatibility, drug loading efficiency, and drug release kinetics were evaluated in vitro for targeted and controlled drug delivery. Spherical core-shell nanoparticles with a diameter of 100 nm showed significantly lower systemic toxicity than did bare MNPs, as well as doxorubicin encapsulation efficiency of 72%, and significantly higher doxorubicin release at 41°C compared with 37°C, demonstrating their temperature sensitivity. Released drugs were also active in destroying prostate cancer cells (JHU31). Furthermore, the nanoparticle uptake by JHU31 cells was dependent on dose and incubation time, reaching saturation at 500 μg/mL and 4 hours, respectively. In addition, magnetic resonance imaging capabilities of the particles were observed using agarose platforms containing cells incubated with nanoparticles. Future work includes investigation of targeting capability and effectiveness of these nanoparticles in vivo using animal models.From the Clinical EditorIn this paper, previously uncharacterized magnetic nanoparticles were synthesized using silane-coated MNPs as a template for radical polymerization of N-isopropylacrylamide, acrylamide, and allylamine. Various properties of these nanoparticles were evaluated in vitro for targeted drug delivery.     

Gadolinium-doped hollow CeO2-ZrO2 nanoplatform as multifunctional MRI/CT dual-modal imaging agent and drug delivery vehicle

Developing multifunctional nanoparticle-based theranostic platform for cancer diagnosis and treatment is highly desirable, however, most of the present theranostic platforms are fabricated via complicated structure/composition design and time-consuming synthesis procedures. Herein, the multifunctional Gd/CeO₂-ZrO₂/DOX-PEG nanoplatform with single nano-structure was fabricated through a facile route, which possessed MR/CT dual-model imaging and chemotherapy ability. The nanoplatform not only exhibited well-defined shapes, tunable compositions and narrow size distributions, but also presented a well anti-cancer effect and MR/CT imaging ability. Therefore, the Gd/CeO₂-ZrO₂/DOX-PEG nanoplatform could be applied for chemotherapy as well as dual-model MR/CT imaging.     

Targeted near-IR hybrid magnetic nanoparticles for in vivo cancer therapy and imaging

We report the use of immuno-targeted gold–iron oxide hybrid nanoparticles for laser-assisted therapy and for MRI-based imaging as demonstrated in xenograft colorectal cancer tumor model. Immuno-targeted gold–iron oxide nanoparticles selectively accumulate in SW1222 xenograft tumors as compared to the accumulation in non-antigen-expressing tumor xenografts. Effective photothermal treatment using near-IR laser irradiation (808 nm, 5 W cm^? 2) application is shown where > 65% of the antigen-expressing tumor cells presented corrupt extracellular matrix and cytoplasmic acidophilia suggesting effectiveness of nanoparticle-assisted thermal therapy. Cell killing was confirmed by hematoxylin and eosin (H&E) histological staining where scar-like structure containing collagen bundles was observed in the treatment group. Further, systemically injected HNPs were shown to be effective T₂ magnetic resonance (MR) imaging contrast agents, localized and detected at the antigen-expressing xenograft tumors. These findings suggest that the new class of bio-conjugated HNPs exhibits great potential for dual-therapy and diagnostics (theranostics) applications.From the Clinical EditorThis team reports the successful use of immuno-targeted gold-iron oxide hybrid nanoparticles for both laser-assisted therapy and MRI-based imaging in a xenograft colorectal cancer tumor model, demonstrating strong potentials for dual applications in cancer diagnosis and therapy.     

A Functional Iron Oxide Nanoparticles Modified with PLA-PEG-DG as Tumor-Targeted MRI Contrast Agent

Purpose

Tumor targeting could greatly promote the performance of magnetic nanomaterials as MRI (Magnetic Resonance Imaging) agent for tumor diagnosis. Herein, we reported a novel magnetic nanoparticle modified with PLA (poly lactic acid)-PEG (polyethylene glycol)-DG (D-glucosamine) as Tumor-targeted MRI Contrast Agent.

Methods

In this work, we took use of the D-glucose passive targeting on tumor cells, combining it on PLA-PEG through amide reaction, and then wrapped the PLA-PEG-DG up to the Fe₃O₄@OA NPs. The stability and anti phagocytosis of Fe₃O₄@OA@PLA-PEG-DG was tested in vitro; the MRI efficiency and toxicity was also detected in vivo.

Results

These functional magnetic nanoparticles demonstrated good biocompatibility and stability both in vitro and in vivo. Cell experiments showed that Fe₃O₄@OA@PLA-PEG-DG nanoparticles exist good anti phagocytosis and high targetability. In vivo MRI images showed that the contrast effect of Fe₃O₄@OA@PLA-PEG-DG nanoparticles prevailed over the commercial non tumor-targeting magnetic nanomaterials MRI agent at a relatively low dose.

Conclusions

The DG can validly enhance the tumor-targetting effect of Fe₃O₄@OA@PLA-PEG nanoparticle. Maybe MRI agents with DG can hold promise as tumor-targetting development in the future.

     

Synergic fabrication of multifunctional liposomes nanocomposites for improved radiofrequency ablation combination for liver metastasis cancer therapy

The field of biomedical research has recently been interested in nanoplatforms with various functionalities, such as cancer drug carriers and MRI and optical imaging, as well as thermal treatment, among other things. As a result of the present investigation, a unique multifunctional liposome (MFL) was established in this investigation. Using radiofrequency-induced imaging and drug release based on magnetic field impact, a dual drug delivery targeted with tumor multi-mechanism treatment was made more effective. The C60 (fullerene) surface was coated with iron nanocomposites to establish the proposed nanosystems, and PEGylation was used (Fe₃O₄-C60-PEG₂₀₀₀). For fullerene radiofrequency-triggered drug release, thermosensitive DPPC liposomes with folate-DSPE-PEG₂₀₀₀ enveloped the binary nanosystems and doxorubicin (DOX). The in vitro cytotoxicity of the nanocomposites was confirmed by the liver metastasis in HT-29 colon cancer cells using radiofrequency. The flow cytometry analysis confirmed the apoptosis cell death mechanism. The thermal treatment combined chemotherapeutic MFL nano framework transformed radiofrequency radiation from thermoresponsive liposomes, which was noticed both in vivo and in vitro. Due to their superior active tumor targeting and magnetic targeting characteristics, the MFL could also selectively destroy cancerous liver cells in highly co-localized targets.     

Doxorubicin Loading,Release, and Stability of Polyamidoamine Dendrimer-Coated Magnetic Nanoparticles

Nanotechnology is a promising alternative to overcome the limitations of classical chemotherapy. As a novel approach, dendrimer-coated magnetic nanoparticles (DcMNPs) maintain suitable drug delivery system because of their buildup of functional groups, symmetry perfection, nanosize, and internal cavities. They can also be targeted to the tumor site in a magnetic field. The aim of this study is to obtain an effective targeted delivery system for doxorubicin, using polyamidoamine (PAMAM) DcMNPs. Different generations (G₂, G₃, G₄, and G₇) of PAMAM DcMNPs were synthesized. Doxorubicin loading, release, and stability efficiencies in these nanoparticles (NPs) were studied. The results showed that low-generation NPs obtained in this study have pH-sensitive drug release characteristics. G₄DcMNP, which releases most of the drug in lower pH, seems to be the most suitable generation for efficient Doxorubicin delivery. Furthermore, application of doxorubicin-loaded G₄DcMNPs may help to overcome doxorubicin resistance in MCF-7 cells. On the contrary, G₂ and G₃DcMNPs would be suitable for the delivery of drugs such as vinca alkaloids (Johnson IS, Armstrong JG, Gorman M, Burnett JP. 1963. Cancer Res 23:1390–1427.) and taxenes (Clarke SJ, Rivory LP. 1999. Clin Pharmacokinet 36(2):99–114.), which show their effects in cytoplasm. The results of this study can provide new insights in the development of pH-sensitive targeted drug delivery systems to overcome drug resistance during cancer therapy.     

Environmentally Responsive Dual-Targeting Nanoparticles: Improving Drug Accumulation in Cancer Cells as a Way of Preventing Anticancer Drug Efflux

Drug targeting and stimuli-responsive drug release are 2 active areas of cancer research and hold tremendous potential in the management of cancer drug resistance. In this study, I addressed this issue and focused on the synthesis and characterization of pH-responsive Fe₃O₄@SiO₂(FITC)-BTN/folic acid/DOX multifunctional nanoparticles aiming to increase drug accumulation in malignancies with both dual active targeting and endosomal drug release properties. Dye-doped silica magnetic-fluorescent composite was constructed by a simple coprecipitation of Fe⁺²/Fe⁺³ salts followed by sol-gel formation and dual-targeting function was obtained by conjugating folate and biotin moieties on the silica surface of nanoparticles via an esterification reaction. Doxorubicin was then successfully attached on the amine-functionalized nanoparticles using a pH-sensitive Schiff-base formation. The physicochemical characterization of the structure was performed by dynamic light scattering, zeta potential measurement, X-ray diffraction, Fourier transform infrared spectroscopy, electron microscopy techniques, and an in vitro pH-dependent release study. Cellular uptake and cytotoxicity experiments demonstrated an enhanced intracellular delivery and reduction of cancer cell viability in the cervical carcinoma HeLa cell line. Furthermore, proapoptotic studies showed that the nanoparticles increased the apoptotic rates within the same cancer cells. The preliminary cell tests confirm the potential of these multifunctional nanoparticles against the development of drug resistance in cancer cells.