Synthesis and Biological Response of Size-Specific, Monodisperse Drug-Silica Nanoconjugates

Sep 21, 2026

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Drug-containing nanoparticles (NPs) with monodisperse, size-controlled distributions are crucial for reliable drug-delivery studies. Evidence indicates that NPs smaller than 50 nm can outperform larger systems in both vitro and in vivo settings. Fabricating monodisperse, drug-loaded NPs with discrete sizes remains challenging. Here, a scalable production method yields drug-silica nanoconjugates with monodisperse sizes down to ~20 nm, demonstrating superior tumor accumulation, penetration, and cellular internalization.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

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Article Overview

Scheme 1: Drug/dye-silica nanoconjugate

Synthesis and Biological Response of Size-Speciﬁc, Monodisperse Drug􀀁Silica Nanoconjugates Li Tang,† Timothy M. Fan,‡ Luke B. Borst,§ and Jianjun Cheng†,* †Department of Materials Science and Engineering and ‡Department of Veterinary Clinical Medicine, University of Illinois at Urbana;Champaign, Urbana, Illinois 61801, United States and §Department of Population Health and Pathobiology, North Carolina State University, Raleigh, North Carolina 27606, United States Nanomedicines in the form of poly mer􀀁drug conjugates, micelles, nanoparticles (NPs), and vesicles have been extensively studied in the past 2􀀁3 decades for drug and gene delivery applications.1􀀁9 Although promising, the clinical translation of nanomedicines has proven very diﬃcult.3 Numerous studies have been designed and performed using nanomedicine as a new modality for improved cancer treatment. However, very few nanomedicines have ever been clinically evaluated and even less have been approved for clinical cancer treatment. 10,11 Although no generalized pathway exists for the clinical translation of nanomedicine, there is a consensus that a clinically applicable nanomedicine should possess controlled physicochemical and pharmacological properties. Speciﬁcally, such nanomedicine should have controlled size with low size dispersity, high drug loading, high loading eﬃciency, controlled drug release kinetics, and suﬃcient stability and capability of staying nonaggregated in biological media. It should also be easily manufactured at a large scale, from grams up to kilogram scale, and lyophilized to form solid formulation. Very few nanomedicine systems can meet all of these formulation requirements that are critical to their clinical translation. There has been growing interest in using nanomedicines for targeted or personalized cancer therapy. 1,2 Accumulating evidence shows that the size of nanomedicine plays a vital role in controlling systemic and lymphatic biodistribution, tumor targeting and penetration, and cellular internalization of drug delivery vehicles. 12􀀁23 NPs with size controlled within 20􀀁60 nm have been particularly interesting and actively pursued because some recent studies showed that NPs within this size range have distinct ABSTRACT Drug-containing nanoparticles (NPs) with monodisperse, controlled particle sizes are highly desirable for drug delivery. Accumulating evidence suggests that NPs with sizes less than 50 nm demonstrate superior performance in vitro and in vivo. However, it is diﬃcult to fabricate monodisperse, drug-containing NPs with discrete sizes required for studying and characterizing existing relationships among particle size, biologic processing, and therapeutic functionality. Here, we report a scalable process of fabricating drug􀀁silica conjugated nanoparticles, termed drug􀀁silica nanoconjugates (drug-NCs), which possess monodisperse size distributions and desirable particle sizes as small as 20 nm. We ﬁnd that 20 nm NCs are superior to their 50 and 200 nm NC analogues by 2􀀁5-and 10􀀁20-fold, respectively, with regard to tumor accumulation and penetration and cellular internalization. These fundamentalﬁndings underscore the importance and necessity of further miniaturizing nanomedicine size for optimized drug delivery applications. KEYWORDS: silica nanoparticle . nanoconjugates . chemotherapeutics . nanomedicine. drug delivery . cancer therapy . tumor penetration . cell uptake . nanoparticle biodistribution biodistribution, tumor penetration, and cellular traﬃcking properties that are critical to the in vivo use of nanomedicine. For instance, Tseng and his team reported that 30 nm NPs were able to drain into the local auxiliary lymph nodes with high eﬃciency after footpad administration of NPs while the 100 nm NPs were nearly undetectable in these tissues.24 Chan and his co-workers reported that 20 and 60 nm gold NPs, as model drug delivery systems, permeated tumor tissues much more rapidly than 100 nm particle

FAQs

What problem does the paper address in nanomedicine delivery?

Clinically translating nanomedicines is difficult because only few systems meet strict formulation needs such as controlled size, low dispersity, high drug loading and efficient release, stability in biological media, and scalable manufacturing. Additionally, existing methods struggle to produce monodisperse, drug-containing NPs with discrete sizes below 50 nm.

What are drug-silica nanoconjugates (drug-NCs) and how are they prepared?

The study reports a scalable process to fabricate drug-silica conjugated nanoparticles called drug-silica nanoconjugates (drug-NCs). The synthesis uses approaches such as the Stöber method or reverse microemulsion method, followed by in situ surface PEGylation and appropriate reagent choices depending on the method.

How do the ~20 nm nanoconjugates compare with larger sizes?

The paper finds that 20 nm nanoconjugates outperform 50 and 200 nm analogues by multiple-fold in tumor accumulation and penetration and in cellular internalization, highlighting the importance of miniaturizing nanomedicine size for optimized delivery.

Sep 21, 2026

Uploaded by Bulrr