Intelligent Probabilistic System for Digital Tracing Cellular Origin of Individual Clinical Extracellular Vesicles.

Extracellular vesicles (EVs) are small vesicles secreted by various cell types to mediate cell-to-cell communication through the transfer of macromolecules. EVs carry multiple cargo molecules that reflect the origins of their donor cells; thus, they can be considered reliable biomarkers for early cancer diagnosis. However, the diverse cellular origin of EV masks the detection signals generated by both tumor- and nontumor-derived cells. Thereby, the capability to recognize the cellular origin of EVs is the prerequisite for their diagnostic applications. In the present study, we develop an intelligent probabilistic system for tracing the cellular origin of individual EVs using single-molecule multicolor imaging. Through the analysis of the expression profile of two typical membrane protein markers, CD9 and CD63, on single EVs, accurate and rapid probabilistic recognition of EVs derived from individual tumor and nontumor cells in clinical samples is achieved. The correlation between cellular origin and surface protein phenotyping on single EVs is also exemplified. The proposed system holds great potential for advancing EVs as reliable clinical indicators and exploring their biological functions.

A polydopamine nanomedicine used in photothermal therapy for liver cancer knocks down the anti-cancer target NEDD8-E3 ligase ROC1 (RBX1).

Knocking down the oncogene ROC1 with siRNA inhibits the proliferation of cancer cells by suppressing the Neddylation pathway. However, methods for delivering siRNA in vivo to induce this high anticancer activity with low potential side effects are urgently needed. Herein, a folic acid (FA)-modified polydopamine (PDA) nanomedicine used in photothermal therapy was designed for siRNA delivery. The designed nanovector can undergo photothermal conversion with good biocompatibility. Importantly, this genetic nanomedicine was selectively delivered to liver cancer cells by FA through receptor-mediated endocytosis. Subsequently, the siRNA cargo was released from the PDA nanomedicine into the tumor microenvironment by controlled release triggered by pH. More importantly, the genetic nanomedicine not only inhibited liver cancer cell proliferation but also promoted liver cell apoptosis by slowing ROC1 activity, suppressing the Neddylation pathway, enabling the accumulation of apototic factor ATF4 and DNA damage factor P-H2AX. Combined with photothermal therapy, this genetic nanomedicine showed superior inhibition of the growth of liver cancer in vitro and in vivo. Taken together, the results indicate that this biodegradable nanomedicine exhibits good target recognition, an effective pH response, application potential for genetic therapy, photothermal imaging and treatment of liver cancer. Therefore, this work contributes to the design of a multifunctional nanoplatform that combines genetic therapy and photothermal therapy for the treatment of liver cancer.

Paclitaxel-loaded and folic acid-modified PLGA nanomedicine with glutathione response for the treatment of lung cancer.

Targeted delivery and smart response of nanomedicine hold great promise for improving the therapeutic efficacy and alleviating the side effects of chemotherapy agents in cancer treatment. However, availability of only a few studies that discuss organic nanomedicines with these properties limits the development prospects of nanomedicines. In the present study, folic acid (FA)-targeted delivery and glutathione (GSH) smart responsive nanomedicine were rationally designed for paclitaxel (PTX) delivery for the treatment of lung cancer. Compared with other stimuli-responsive nanomedicines, this nanocarrier was not only sensitive to biologically relevant GSH for on-demand drug release but also biodegradable into biocompatible products after fulfilling its delivery task. The nanomedicine first entered tumor cells via FA and its receptor-mediated endocytosis. After the lysosomal escape, poly(lactic-co-glycolic acid) (PLGA) nanomedicine was triggered by a higher level of GSH and released its cargo into the tumor microenvironment. In vitro and in vivo results revealed that the PLGA nanomedicine not only inhibited the proliferation and promoted the apoptosis of lung cancer cells significantly but also possessed less toxic side effects when compared with free PTX. Therefore, the proposed drug delivery system demonstrates the potential of a multifunctional nano-platform to enhance bioavailability and reduce the side effects of chemotherapy agents.

Investigating the immune mechanism of natural products in the treatment of lung cancer.

With the deepening of people's understanding of lung cancer, the research of lung cancer immunotherapy has gradually become the focus of attention. As we all know, the treatment of many diseases relies on the rich sources, complex and varied compositions and wide range of unique biological properties of natural products. Studies have shown that natural products can exert anticancer effects by inducing tumor cell death, inhibiting tumor cell proliferation, and enhancing tumor cell autophagy. More notably, natural products can adjust and strengthen the body's immune response, which includes enhancing the function of NK cells and promoting the differentiation and proliferation of T lymphocytes. In addition, these natural products may enhance their anticancer effects by affecting inhibitory factors in the immune system, hormone levels, enzymes involved in biotransformation, and modulating other factors in the tumor microenvironment. The importance of natural products in lung cancer immunotherapy should not be underestimated. However, the specific links and correlations between natural products and lung cancer immunity are not clear enough, and further studies are urgently needed to clarify the relationship between the two. In this paper, we will focus on the correlation between natural products and lung cancer immune responses, with a view to providing new research perspectives for immunotherapy of lung cancer.

EXPRESS: Landmark Publications in Analytical Atomic Spectrometry: Fundamentals and Instrumentation Development.

The almost-two-centuries history of spectrochemical analysis has generated a body of literature so vast that it has become nearly intractable for experts, much less for those wishing to enter the field. Authoritative, focused reviews help to address this problem but become so granular that the overall directions of the field are lost. This broader perspective can be provided partially by general overviews but then the thinking, experimental details, theoretical underpinnings and instrumental innovations of the original work must be sacrificed. In the present compilation, this dilemma is overcome by assembling the most impactful publications in the area of analytical atomic spectrometry. Each entry was proposed by at least one current expert in the field and supported by a narrative that justifies its inclusion. The entries were then assembled into a coherent sequence and returned to contributors for a round-robin review.

Smart mesoporous SiO2 nanoparticles for the DNAzyme-induced multiplexed release of substrates.

The fluorescent dyes methylene blue, MB(+), and thionine, Th(+), can be trapped in the pores of mesoporous silica, MP-SiO(2), by means of functional nanostructures consisting of the Mg(2+)- or Zn(2+)-dependent DNAzyme sequences. In the presence of Mg(2+) or Zn(2+) ions the respective DNAzymes are activated, leading to the specific cleavage of the respective caps, and the selective release of MB(+) or Th(+). The enlargement of the conserved loop domains of the Mg(2+)- or Zn(2+)-dependent DNAzyme sequences with foreign nucleotides prohibits the formation of active DNAzymes and eliminates the release of the respective dyes. This is due to the flexibility of the loops that lacks affinity for the association of the ions. The insertion of aptamer sequences (e.g., the adenosine-5'-triphosphate (ATP) aptamer) or ion-binding sequences (e.g., T-rich Hg(2+) ion-binding domains) as foreign components to the loop regions allows the formation of active Mg(2+)- or Zn(2+)-dependent DNAzyme structures through the cooperative formation of aptamer-ATP complexes or T-Hg(2+)-T bridges. These aptamer-substrate complexes or T-Hg(2+)-T bridges allosterically stabilize and activate the DNAzymes, thus allowing the selective release of the fluorescent substrates MB(+) or Th(+). The metal ion-driven DNAzyme release of substrates from the pores of MP-SiO(2), and particularly the allosteric activation of the DNAzymes through cooperative aptamer-substrate complexes or metal-ion bridges, has important future nanomedical implications for targeted release of drugs. This is demonstrated with the triggered release of the anticancer drug, doxorubicin, by the Mg(2+)-DNAzyme-locked pores or by the aptamer-ATP complex-triggered activation of the Mg(2+)-dependent DNAzyme.

Helquat-induced chiroselective aggregation of Au NPs.

Au nanoparticles (NPs) are functionalized with chiral (R) or (S) binaphthol phenylboronic acid ligands, (1a) or (1b). The (R)- or (S)-binaphthol phenylboronic acid ligands form donor-acceptor complexes with the chiral dicationic helicene, helquat (P)-HQ(2+) or (M)-HQ(2+), (2a) or (2b). The association constants between (1a)/(2a) and (1a)/(2b) correspond to (7.0 ± 0.5) × 10(5) M(-1) and (2.5 ± 0.3) × 10(5) M(-1), respectively, whereas the association constants between (1b)/(2b) and (1b)/(2a) correspond to (4.0 ± 0.5) × 10(5) M(-1) and (1.8 ± 0.3) × 10(5) M(-1), respectively. Chiroselective aggregation of chiral binaphthol phenylboronic acid-capped Au NPs triggered by the chiral helquats, is demonstrated.

Combined chemo-immuno-photothermal therapy based on ursolic acid/astragaloside IV-loaded hyaluronic acid-modified polydopamine nanomedicine inhibiting the growth and metastasis of non-small cell lung cancer.

Combining chemotherapy and immunotherapy is a promising strategy for the treatment of non-small cell lung cancer (NSCLC) metastasis. However, platinum-based chemotherapeutics and immune checkpoint blockade-based cancer immunotherapy have toxic side effects and limitations. Ursolic acid (UA) and astragaloside IV (AS-IV) are natural compounds with anticancer activity sourced from Traditional Chinese medicine (TCM). However, their poor water solubilities and targeted deletions limit their medicinal value. In this study, we fabricated hyaluronic acid (HA)-modified UA/(AS-IV)-loaded polydopamine (PDA) nanomedicine (UA/(AS-IV)@PDA-HA) with a high yield at a low cost via simple synthesis. This represents a novel multifunctional nanomedicine that combines chemotherapy, photothermal therapy (PTT), and immunotherapy with an active tumor-targeting ability. The as-prepared nanomedicine not only increased the aqueous solubilities of UA and AS-IV, but also improved their active targeting abilities. HA binds specifically to the overexpressed cluster of differentiation 44 (CD44) on the surface of most cancer cells, thereby improving drug targeting. While evaluating the anticancer effect of UA/(AS-IV)@PDA-HA in vitro and in vivo, the PDA nanodelivery system significantly improved UA-mediated cytotoxicity and anti-metastatic ability against NSCLC cells. In addition, the system also improved the AS-IV-mediated self-immune response of tumor-related antigens, which further inhibited the growth and distant metastasis of NSCLC. Further, PDA nanomaterial-mediated PTT inhibited tumor growth substantially. UA/(AS-IV)@PDA-HA not only significantly eradicated the primary tumor but also strongly inhibited the distant metastasis of NSCLC in vitro and in vivo. Thus, it has immense potential for development as an efficient anti-metastatic agent for NSCLC.

Fluorescence detection of DNA, adenosine-5'-triphosphate (ATP), and telomerase activity by zinc(II)-protoporphyrin IX/G-quadruplex labels.

The zinc(II)-protoporphyrin IX (ZnPPIX) fluorophore binds to G-quadruplexes, and this results in the enhanced fluorescence of the fluorophore. This property enabled the development of DNA sensors, aptasensors, and a sensor following telomerase activity. The DNA sensor is based on the design of a hairpin structure that includes a "caged" inactive G-quadruplex sequence. Upon opening the hairpin by the analyte DNA, the resulting fluorescence of the ZnPPIX/G-quadruplex provides the readout signal for the sensing event (detection limit 5 nM). Addition of Exonuclease III to the system allows the recycling of the analyte and its amplified analysis (detection limit, 200 pM). The association of the ZnPPIX to G-quadruplex aptamer-substrate complexes allowed the detection of adenosine-5'-triphosphate (ATP, detection limit 10 µM). Finally, the association of ZnPPIX to the G-quadruplex repeat units of telomers allowed the detection of telomerase activity originating from 380 ± 20 cancer 293T cell extract.

Synergistic chemo-photothermal and ferroptosis therapy of polydopamine nanoparticles for esophageal cancer.

Aim: To develop synergistic chemo-photothermal and ferroptosis therapy nanoparticles to improve the efficacy of treatment for esophageal cancer. Materials & methods: Fe3O4@PDA-HCPT nanoparticles (NPs) were constructed and characterized. Their synergistic antitumor effects were evaluated in EC1 and EC109 esophageal cancer cells as well as in esophageal cancer-bearing mice. Results: In vitro and in vivo experiments showed that Fe3O4@PDA-HCPT NPs exhibited significant tumor inhibition and excellent diagnostic properties. The killing ability of tumor cells was significantly enhanced after irradiation. Conclusion: Synergistic application of the three therapies effectively inhibited tumor growth and exhibited potent antitumor effects, providing strong support for developing nanoparticles with synergistic antitumor effects of multiple therapies.

Synergistic treatment with multiple therapies has been shown to be a promising strategy for cancer treatment. Here, the authors designed Fe₃O₄@PDA-HCPT NPs composed of Fe₃O₄, polydopamine and the chemotherapy drug 10-hydroxycamptothecin. The authors achieved synergistic antitumor treatment with chemo-photothermal and ferroptosis therapy guided by T2-weighted MRI. In vitro and in vivo experiments showed that Fe₃O₄@PDA-HCPT NPs exhibited significant tumor inhibition and excellent diagnostic properties, which supports the development of relevant synergistic tumor therapies.

Camptothecin-Loaded and Manganese Dioxide-Coated Polydopamine Nanomedicine Used for Magnetic Resonance Imaging Diagnosis and Chemo-Photothermal Therapy for Lung Cancer.

Introduction: Camptothecin (CPT) is a cytotoxic quinolone alkaloid (isolated from a traditional Chinese medicine Camptotheca acuminata), used for the treatment of various malignancies, which inhibits DNA topoisomerase I (Topo I). However, its drawbacks, such as poor water solubility, stability, and highly toxic side effects, limit its clinical application. Therefore, CPT needs to be prepared as a nanomedicine to improve solubility, reduce side effects, and synergize with other therapies to improve efficacy. Methods: In this work, we constructed CPT NPs (nanoparticles), which were CPT-loaded and manganese dioxide (MnO2)-coated polydopamine (PDA) nanomedicine. In vitro, we explored the antitumor effect including CPT NPs-induced cell proliferation inhibition, apoptosis and ferroptosis for tumor cell lines. In vivo, we established LLC tumor-bearing mice model to evaluate their tumor imaging and anticancer effects. Results: CPT NPs improve the water solubility and stability of CPT and reduce its toxic effects. It has good biocompatibility, excellent photothermal conversion ability for photothermal therapy (PTT) and pH release in the tumor microenvironment. It can inhibit tumor cell proliferation, induce apoptosis and result in ferroptosis of tumor cells. More significantly, this nanomedicine can provide information for the location and diagnosis of tumors via magnetic resonance imaging. In general, the nanomedicine integrated with diagnosis and treatment has excellent anticancer effect. Discussion: Altogether, this nanomedicine possesses the ability to diagnose and therapy through magnetic resonance imaging and chemo-photothermal therapy, respectively. In addition, the integrated diagnosis and treatment nanomedicine has potential clinical application prospects through treating lung cancer with high efficiency and low side effect. It can support the construction of related nano-delivery systems.

Advances in Antitumor Nano-Drug Delivery Systems of 10-Hydroxycamptothecin.

10-Hydroxycamptothecin (HCPT) is a natural plant alkaloid from Camptotheca that shows potent antitumor activity by targeting intracellular topoisomerase I. However, factors such as instability of the lactone ring and insolubility in water have limited the clinical application of this drug. In recent years, unprecedented advances in biomedical nanotechnology have facilitated the development of nano drug delivery systems. It has been found that nanomedicine can significantly improve the stability and water solubility of HCPT. NanoMedicines with different diagnostic and therapeutic functions have been developed to significantly improve the anticancer effect of HCPT. In this paper, we collected reports on HCPT nanomedicines against tumors in the past decade. Based on current research advances, we dissected the current status and limitations of HCPT nanomedicines development and looked forward to future research directions.

Acacetin inhibits invasion, migration and TGF-ß1-induced EMT of gastric cancer cells through the PI3K/Akt/Snail pathway.

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) is a pivotal cellular phenomenon involved in tumour metastasis and progression. In gastric cancer (GC), EMT is the main reason for recurrence and metastasis in postoperative patients. Acacetin exhibits various biological activities. However, the inhibitory effect of acacetin on EMT in GC is still unknown. Herein, we explored the possible mechanism of acacetin on EMT in GC in vitro and in vivo. METHODS: In vitro, MKN45 and MGC803 cells were treated with acacetin, after which cell viability was detected by CCK-8 assays, cell migration and invasion were detected by using Transwell and wound healing assays, and protein expression was analysed by western blots and immunofluorescence staining. In vivo, a peritoneal metastasis model of MKN45 GC cells was used to investigate the effects of acacetin. RESULTS: Acacetin inhibited the proliferation, invasion and migration of MKN45 and MGC803 human GC cells by regulating the expression of EMT-related proteins. In TGF-ß1-induced EMT models, acacetin reversed the morphological changes from epithelial to mesenchymal cells, and invasion and migration were limited by regulating EMT. In addition, acacetin suppressed the activation of PI3K/Akt signalling and decreased the phosphorylation levels of TGF-ß1-treated GC cells. The in vivo experiments demonstrated that acacetin delayed the development of peritoneal metastasis of GC in nude mice. Liver metastasis was restricted by altering the expression of EMT-related proteins. CONCLUSION: Our study showed that the invasion, metastasis and TGF-ß1-induced EMT of GC are inhibited by acacetin, and the mechanism may involve the suppression of the PI3K/Akt/Snail signalling pathway. Therefore, acacetin is a potential therapeutic reagent for the treatment of GC patients with recurrence and metastasis.

A sensitive choline biosensor using Fe3O4 magnetic nanoparticles as peroxidase mimics.

A sensitive choline biosensor using Fe(3)O(4) magnetic nanoparticles and a choline oxidase modified gold electrode was developed. Fe(3)O(4) magnetic nanoparticles as peroxidase mimics used in the choline biosensor can not only improve the sensitivity of the response signal, but also possess the favorable properties of stability, magnetic separation and easy preparation, etc. When using the reduction currents of square wave voltammetry as the detection signals, the interferences of ascorbic acid and uric acid to the choline biosensor can be reduced effectively. The reduction currents of the square wave voltammetry were increased with the logarithm values of the choline chloride concentration (from 10(-9) to 10(-2) M), the detection limit was estimated to be 0.1 nM (S/N = 3). This choline biosensor also exhibited favorable selectivity and stability in the determination of choline chloride.

Cinobufagin-Loaded and Folic Acid-Modified Polydopamine Nanomedicine Combined With Photothermal Therapy for the Treatment of Lung Cancer.

Cinobufagin is used as a traditional Chinese medicine for cancer therapy. However, it has some disadvantages, such as poor water solubility, short circulating half-life, and low bioavailability. In the present study, a targeted delivery and smart responsive polydopamine (PDA)-based nanomedicine for delivering cinobufagin was rationally designed to improve the anticancer efficacy of the compound for the treatment of lung cancer. The modification of the nanomedicine using folic acid first mediated tumor targeting via the interaction between folic acid and its receptors on tumor cells. After lysosomes escape, the PDA nanomedicine was triggered by the low pH and released its cargo into the tumor microenvironment. The nanomedicine had a better therapeutic effect against lung cancer when used in combination with photothermal therapy. Compared with other nanomedicines used with photothermal therapy, this nanocarrier was not only sensitive to biologically low pH levels for on-demand drug release, but was also biodegradable, breaking down into biocompatible terminal products. Therefore, the proposed drug delivery system with targeted delivery and smart release demonstrated potential as a multifunctional nanoplatform that can enhance the bioavailability and reduce the side effects of chemotherapeutic agents.

Distinction of single base mismatches in duplex DNA using methylene blue as optical indicator.

A simple and sensitive approach for the recognition of single base mismatches in duplex DNA was developed. The single base mismatched double-strand (ds) DNA and the completely complementary dsDNA can quench the fluorescence of methylene blue to the different values, so the point mutation dsDNA can be identified from the duplex DNA effectively. The fluorescence intensity was decreased with the increasing dsDNA concentration in the range of 10~1000 nM, the detection limit was estimated to be 50 nM (S/N = 3). The contrast experiment showed that this method possesses the universality for the distinction of other single base mismatches in duplex DNA. Moreover, the interaction mechanism between methylene blue and dsDNA was also discussed in detail. The UV-Visible absorption and the fluorescence experiments indicated that the interaction of methylene blue and dsDNA had at least two effective modes: the electrostatic binding and the intercalation binding. When more methylene blue molecules bound onto mismatched dsDNA, the fluorescence intensity of methylene blue would decrease to a lower value than that of completely complementary dsDNA. Therefore, single base mismatched dsDNA can be recognized from duplex DNA effectively.

An anticancer agent-loaded PLGA nanomedicine with glutathione-response and targeted delivery for the treatment of lung cancer.

Stimuli response or controlled release is a new research hotspot in nanomedicine; however, there is scarce research on organic nanomedicines with stimuli responses, which limits their practical biological applications. In addition, homoharringtonine (HHT) has been used as an effective anticancer agent, but reducing its toxicity and side effects is an urgent problem to be solved. Herein, an EGFR (epidermal growth factor receptor) aptamer-modified HHT-loaded PLGA-SS-PEG nanomedicine was developed. The nanomaterial possesses spherical morphology and admirable biocompatibility. After targeted endocytosis in tumour cells via the selective recognition between EGFR and its aptamer, the PLGA nanomedicine is triggered by a high GSH level and releases its cargo in lung cancer cells. The in vitro and in vivo results reveal that the PLGA nanomedicine not only inhibited the proliferation and promoted the apoptosis of lung cancer cells, but also possessed better therapeutic efficacy and less toxic side effects compared with the free anticancer agent. Consequently, this study provides a novel approach to construct a biodegradable nanomedicine with targeted recognition and stimuli response. Moreover, it inhibited the proliferation of lung cancer cells with high efficiency and low toxicity. Importantly, the PLGA nanomedicine demonstrates encouraging potential as a multifunctional nano-system applicable for cancer therapy.

Real-time study of genomic DNA structural changes upon interaction with small molecules using dual-polarization interferometry.

The structural changes of genomic DNA upon interaction with small molecules have been studied in real time using dual-polarization interferometry (DPI). Native or thermally denatured DNA was immobilized on the silicon oxynitride surface via a preadsorbed poly(ethylenimine) (PEI) layer. The mass loading was similar for both types of DNA; however, native DNA formed a looser and thicker layer due to its rigidity, unlike the more flexible denatured DNA, which mixed with PEI to form a denser and thinner layer. Ethidium bromide (EtBr), a classical intercalator, induced the large thickness decrease and density increase of native DNA (double-stranded), but a slight increase in both the thickness and density of denatured DNA (partial single-stranded). Spermine that electrostatically binds DNA induced the increase in layer thickness and decrease in the density of both native and denatured DNA. However, the looser structure of native DNA made it more accessible to spermine, leading to a higher binding amount and larger thickness increase. For native DNA, EtBr induced a slow and less reversible contraction of DNA owing to intercalation, while spermine induced a fast and reversible expansion of DNA owing to electrostatic interaction. DPI offers an effective means for real-time study of DNA structural changes during the interactions.

Smart and dual-targeted BSA nanomedicine with controllable release by high autolysosome levels.

Targeting modifications and smart responsiveness of nanomedicines can enable anticancer drugs to be selectively delivered to and controllably released in tumour cells or tissues, which can reduce the treatment's toxicity and side effects. Good biocompatibility is crucial for the clinical application of any nanomedicine. In this study, a double-targeting molecule, an RGD peptide- and 4-(2-aminoethyl) morpholine-modified, doxorubicin (DOX)-loaded bovine serum albumin (BSA) nanomedicine, that can be controllably released by the high levels of autophagic lysosomes in tumour cells was developed. The size of the spherical BSA nanoparticles is approximately 60 nm. In vitro experiments indicated that the RGD peptide- and 4-(2-aminoethyl) morpholine-modified, DOX-loaded BSA nanomedicine has a better therapeutic effect than free DOX. In vivo experiments suggested that the BSA nanomedicine can successfully suppress the progression of PC9 xenograft tumours. This phenomenon may be attributable to the endocytosis of a relatively large amount of nanomedicine and the effective release of the loaded chemotherapeutic agent, as induced by high levels of autolysosomes. Collectively, the results of this study provide a smart approach for increasing therapeutic efficacy using a double-targeting molecule-modified BSA nanomedicine.

Cetuximab-modified mesoporous silica nano-medicine specifically targets EGFR-mutant lung cancer and overcomes drug resistance.

Drug resistance to tyrosine kinase inhibitor (TKI) is the main obstacle for efficient treatment of epidermal growth factor receptor (EGFR)-mutant lung cancer patients. Here we design a cetuximab-capped mesoporous silica nanoparticle (MP-SiO2 NP) as the drug carrier to specifically target EGFR-mutant lung cancer cells and efficiently release loaded drugs including doxorubicin and gefitinib. This innovative nano-medicine can specifically target lung cancer cells with high EGFR expression rather than those with low EGFR level. Treatment of a gefitinib-resistant cell line derived from PC9 cell (PC9-DR) with the gefitinib-loaded cetuximab-capped MP-SiO2 NP showed a significant inhibition of cell growth. Moreover, this nano-medicine successfully suppressed the progression of PC9-DR xenograft tumors. This tumor suppression was due to the endocytosis of large amount of nano-medicine and the effective gefitinib release induced by high glutathione (GSH) level in PC9-DR cells. Collectively, our study provides a novel approach to overcome EGFR-TKI resistance using cetuximab modified MP-SiO2 NP, which holds strong potential for effective management of EGFR-mutant lung cancer.