## 1 Introduction  
Molecular-mimetic colloids (MMCs) have garnered substantial attention over the past few decades [1, 2, 3, 4, 5], encompassing a diverse range of entities, such as colloidal molecules [6, 7, 8, 9, 10], colloidal polymers [11, 12, 13], colloidal liquid crystals [14, 15, 16], giant molecules/giant surfactants [17, 18], etc. The major driving forces come from two aspects: (1) The observable dynamics within MMC systems offer novel perspectives and fundamental insights into the behavior of conventional, often invisible molecular systems [19, 20]. (2) Established principles in conventional molecular systems serve as a guiding framework to decipher MMCs with varying length scales and compositions [21]. This reciprocal relationship has propelled the development of assembly frameworks utilizing MMCs as functional building blocks [11, 22], and it has also facilitated the exploration of colloid-based materials [23, 24], including nano-/micromotors [25, 26], interfacial stabilizers [27], nanomedicines [28], superlattices [29], and metamaterials [30], among others. This remarkable progress has spurred efforts to devise new strategies for the design and synthesis of MMCs with near-molecular-level precision, considering both molecular configuration and surface chemistry. The continuously expanding repertoire of programmable MMCs is a significant catalyst for the advancement of future colloid-based materials [31, 32]. Among these, molecular-mimetic nanocolloids (MMNCs), particularly those with sizes ranging from 10 nm to 100 nm, hold the most promise due to their programmable functionality. To date, the majority of MMNCs have been synthesized through self-assembly strategies, such as the polymer-ligand regulation approach (including bio-polymer DNA [33, 34, 35] and synthetic block polymers [8, 13]), nanoconfinedassembly utilizing DNA origami templates [7] or other substrates [36], surface patterning on nanoparticle surfaces [37,38], etc. Nevertheless, the utilization of these MMNCs as building blocks for bulk materials is hampered by challenges associated with relatively low yield and purity. To address the challenges of relatively low yield and purity [22,38] in self-assembly strategies for synthesizing molecular-mimetic nanocolloids (MMNCs), the MMNC total synthesis strategy--inspired by conventional molecular fabrication processes (molecular design and synthesis)--holds the potential to surmount the hurdles encountered in self-assembly-based preparation methods and accelerate the investigation and development of MMNC-based materials [18,39]. Here, we report a novel strategy for the total synthesis of surfactant-mimetic nanocolloids (SMNCs) via the regioselective deposition of silica on bottlebrush polymers (BBPs) (Figure 1). SMNCs exhibit typical amphiphilic characteristics. Moreover, the well-established principles governing amphiphile (surfactant-like) self-assembly can be applied to evaluate the performance of SMNCs. Therefore, the surfactant-mimetic system was selected as a model to illustrate our strategy in this work. Our strategy offers several distinct molecular engineering advantages: (i) The programmable bottlebrush polymers serve as the tail-like component of the final SMNCs. The diverse programmable structural parameters of the BBP tails, such as sidechain length (\(N_{\text{sc}}\), denoted as \(n\) in Figure 1), backbone length (\(N_{\text{bb}}\), denoted as \(b\) in Figure 1), and the chemical composition of sidechains, can significantly expand the SMNC library. BBPs are size-compatible with nanoparticles (NPs) (here, silica NP lobes) and also possess colloidal properties in addition to their polymeric features [40]. (ii) The regioselective deposition of silica is achieved through a modified Stober method that we reported previously [41]. The key lies in using a single polymer chain containing carboxyl moieties as the nucleating center for the hydrolysis and subsequent polycondensation of silanes into silica nanoparticles.